OTAR3088/single-cell_raw · Datasets at Hugging Face

data dict	annotations list
{ "text": "We generated scRNA-seq profiles of duodenal epithelial, immune and parenchymal populations from 35 participants: 21 with CD (16 children, 5 adults) and 14 controls (5 children, 9 adults; Fig. 1 and Supplementary Table 1 ). We used complementary single-cell techniques for adult and pediatric datasets, with ...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 461, "end": 478, "text": "endothelial cells", "labels": [ "Cell" ] } } ] } ]
{ "text": "We analyzed EPCAM epithelial populations from dataset 1. Nine transcriptionally distinct epithelial cell (EC) clusters were identified, representing progenitor, secretory and absorptive lineages along the developmental progression of the crypt–villus axis (Fig. 2a,b , Extended Data Fig. 1a and Supplementar...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 89, "end": 104, "text": "epithelial cell", "labels": [ "Cell" ] } }, { "from_name": "labe...
{ "text": "A LYZ Paneth cell-like population ( MMP7 REG1A SOD3 PLA2G2A ) was also identified (Fig. 2a,b ), although defensin gene expression was not detected. This population expressed PGC , mucins including MUC5AC , MUC1 and MUC6 and AQP5 , suggesting it also contained Brunner’s gland cells or ectopic gastric pylori...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 270, "end": 275, "text": "gland", "labels": [ "Tissue" ] } }, { "from_name": "label", ...
{ "text": "Transit-amplifying (TA) cells were increased in CD, along with enrichment of uniform manifold approximation and projection (UMAP) areas corresponding to EC progenitors (stem cells, TA cells and early enterocytes; Fig. 2c,d ). This persisted in treated celiac disease (TCD; Extended Data Fig. 1b,c ). In para...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 169, "end": 173, "text": "stem", "labels": [ "Tissue" ] } }, { "from_name": "label", ...
{ "text": "Pseudotime analyses identified epithelial developmental trajectories, from undifferentiated progenitor states toward absorptive and secretory lineages (Fig. 2e ). In CD, ECs were shifted to earlier pseudotime states, with loss of mature ECs (Fig. 2f ). CCL25 , encoding the ligand for CCR9 (implicated in CD...	[]
{ "text": "We examined putative EC functions through functional gene-set analysis (Extended Data Fig. 1a ), identifying functions of secretory Paneth-like/Brunner’s gland cells (secreted protein and vesicle pathways), BEST4 enterocytes (chloride/anion channel activity), tuft cells (taste perception) and enteroendocri...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 625, "end": 635, "text": "epithelium", "labels": [ "Tissue" ] } }, { "from_name": "label"...
{ "text": "ECs in ACD upregulated multiple antigen-presentation molecules, including classical HLA class I and class II genes (except HLA-DQ ) and nonclassical genes including HLA-E and HLA-F (Fig. 2h ). Interferon-stimulated genes (types I and II) dominated the epithelial response, including STAT1 (Fig. 2h and Suppl...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 500, "end": 510, "text": "lymphocyte", "labels": [ "Cell" ] } } ] } ]
{ "text": "Some transcriptional changes were cell-type specific. IL32 was highly expressed in ACD by mature enterocytes (Extended Data Fig. 1k ), perhaps regulated by interferons. The reduction of fatty acid catabolism/transport ( APOA1 , FABP2 ), metal ion transport (iron: FTH1 , FTL ; zinc: SLC39A4 ) and carbohydra...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 665, "end": 668, "text": "gut", "labels": [ "Tissue" ] } }, { "from_name": "label", ...
{ "text": "The duodenum, where CD inflammation predominates, has sensory and neurohormonal functions. We extended EEC clustering, revealing multiple transcriptional states, including NEUROG3 progenitors and EEC subtypes, which showed similar CD-related transcriptional changes to other ECs (Extended Data Fig. 2 ). EEC...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 4, "end": 12, "text": "duodenum", "labels": [ "Tissue" ] } }, { "from_name": "label", ...
{ "text": "In adults (dataset 1), CD4 T cells formed subsets dominated by T H 1-polarized and IL-17-producing helper T (T H 17)-polarized effectors, as well as small naive and FOXP3 regulatory populations (Fig. 3a–c and Supplementary Table 6 ). There was a cluster of T FH -like CD4 T cells expressing PDCD1 , BTLA , C...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 27, "end": 34, "text": "T cells", "labels": [ "Cell" ] } }, { "from_name": "label", ...
{ "text": "This T FH -like population in adults and children showed similar phenotypic profiles to those of gut-resident gluten-specific CD4 T cells in CD (Extended Data Fig. 3b ), and expressed TOX2 , CD200 , IL21 and CXCL13 . The cluster showed enrichment of TRBV7-2 , a V-gene enriched in gluten-specific CD4 T cell...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 130, "end": 137, "text": "T cells", "labels": [ "Cell" ] } }, { "from_name": "label", ...
{ "text": "T cell populations showed distinct cytokine and chemokine expression patterns (Extended Data Fig. 3c ). The CD-associated T FH -like population, showed high CXCL13 and IL21 expression, with IFNG and IL21 coexpression (Fig. 3j,k ), similarly to gluten-specific T cells . T FH -like cells expressed TNFSF8 , C...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 0, "end": 6, "text": "T cell", "labels": [ "Cell" ] } }, { "from_name": "label", ...
{ "text": "Oral gluten challenge in CD drives rapid circulating cytokine responses, including IL-2, CXCL8, CXCL10 and IL-6 (ref. ). CXCL8 expression was highest in CCR7 T FH CD4 T cells, CXCL10 was detected in T FH -like CD4 T cells, while IL6 was detected in T reg cells (Extended Data Fig. 3c ). IL2 expression was l...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 113, "end": 116, "text": "ref", "labels": [ "Cell" ] } }, { "from_name": "label", ...
{ "text": "We examined transcription factor (TF), and regulon expression within CD4 subsets, with canonical TFs and regulons of T H 17 and T reg cell function expressed as expected (Extended Data Fig. 3e–g ). IKZF1 and its regulon were upregulated in T FH -like cells, with intermediate expression of RUNX1 , BATF and ...	[]
{ "text": "We examined B cell lineages in dataset 2 (pediatric; Extended Data Fig. 4a,b ). Both IgA and IgM plasma cells were increased in CD (Extended Data Fig. 4c–f ). A population of CXCR5 B cells ( MS4A1 CD19 CD20 ) were present, with a shift toward the CD27 memory B cell phenotype in CD.\nSource paper: PMC121335...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 12, "end": 18, "text": "B cell", "labels": [ "Cell" ] } }, { "from_name": "label", ...
{ "text": "Gene signatures of age-related B cells (an inflammation-associated population in autoimmune disease ), including ITGAM , ITGAX , CD86 and BATF , were expressed most highly in CD27 B cell populations, while a key age-related B cell TF, TBX21 , was highly expressed in cycling B cells (Extended Data Fig. 4b )...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 31, "end": 38, "text": "B cells", "labels": [ "Cell" ] } }, { "from_name": "label", ...
{ "text": "Intestinal myeloid cell populations are impacted by CD and may be involved in antigen presentation and oral tolerance . Myeloid cells (dataset 2) formed 11 transcriptionally distinct clusters, including macrophages, conventional dendritic cells and plasmacytoid dendritic cells (Supplementary Fig. 2a–c ). H...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 203, "end": 214, "text": "macrophages", "labels": [ "Cell" ] } }, { "from_name": "label",...
{ "text": "Intestinal CD8 T cells showed considerable heterogeneity in transcriptional states, with multiple tissue-resident memory CD8 T (T RM ) cells, including an ITGAE IL7R population, a CCL4 CD69 ITGAE population and two subsets of ITGAE T RM cells (Fig. 4 , Extended Data Fig. 5a and Supplementary Table 7 ). The...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 15, "end": 22, "text": "T cells", "labels": [ "Cell" ] } }, { "from_name": "label", ...
{ "text": "We analyzed subsets relevant to CD, including natural killer (NK)-receptor expressing IELs and killer-cell immunoglobulin-like receptor (KIR)-positive CD8 T cells . KLRC1 (NKG2A) was expressed by CCL4 cells, while KLRC2 (NKG2C) was expressed by resident IL7R , T RM (1) and T RM (2) subsets (Extended Data F...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 155, "end": 162, "text": "T cells", "labels": [ "Cell" ] } } ] } ]
{ "text": "T RM (2) and cycling populations were enriched in ACD, but not T RM (1) cells (Fig. 4f,g ). T RM (2) cells were rare in health, but increased to form 20–40% of CD8 T cells in ACD, which persisted in TCD (Fig. 4h ). Natural IELs were reduced in ACD (Extended Data Fig. 5e ). Cycling CD8 T cells increased to ...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 164, "end": 171, "text": "T cells", "labels": [ "Cell" ] } }, { "from_name": "label", ...
{ "text": "As T RM (2) CD8 T cells were increased in proportion and proliferating in ACD, we profiled them in depth (Fig. 5a–e and Extended Data Fig. 6 ). T RM (2) CD8 T cells showed a CD103 tissue-resident phenotype, high GZMA and absent GZMK expression, along with high expression of CXCR6, activation markers ( HLA-...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 16, "end": 23, "text": "T cells", "labels": [ "Cell" ] } }, { "from_name": "label", ...
{ "text": "We examined pseudotime trajectories of tissue-resident clusters with TCR repertoire clonal sharing (T RM (1), T RM (2), IL7R and CCL4 effectors) to infer putative differentiation pathways (Fig. 5a,b,e ). The pseudotime trajectory showed two branches, formed predominantly of T RM (1) cells in branch 1 and T...	[]
{ "text": "We examined cytokine, chemokine and TF expression by CD8 T cell subsets. The predominant CD8 sources of IFNG were CD8 T RM (2) and cycling clusters (Fig. 5c,d and Extended Data Fig. 5g–i ). These populations also expressed the chemokine CCL5 , CD70 and FASLG . Natural IELs (reduced in ACD), produced CCL2 ,...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 57, "end": 63, "text": "T cell", "labels": [ "Cell" ] } } ] } ]
{ "text": "CD8 T cell-induced epithelial damage is thought to be mediated via TCR-independent mechanisms. We hypothesized that CD8 T cell TCR repertoires would be similar in health and disease. Single-cell TCR sequences were examined, which showed expected clonal overlap between tissue-resident populations (Fig. 5e a...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 4, "end": 10, "text": "T cell", "labels": [ "Cell" ] } }, { "from_name": "label", ...
{ "text": "Consequently, we sorted intraepithelial CD8 T cells from 12 adults with and without CD (dataset 3) and performed bulk RNA-seq. This showed significant enrichment of one TRBV segment, TRBV28 , enriched in ACD and TCD, but not controls (Fig. 5g ). TRBV28 was the high-frequency V segment with the highest fold...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 44, "end": 51, "text": "T cells", "labels": [ "Cell" ] } } ] } ]
{ "text": "We validated this by performing bulk TCR repertoire sequencing on 1,068,814 mucosal CD8 T cells from 20 donors with and without CD (dataset 4). Again, TRBV28 was highly upregulated in CD, forming 10% of unique CDR3 sequences in ACD and TCD, versus 2% in controls (Fig. 5h ). TRBV28 was also enriched within ...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 88, "end": 95, "text": "T cells", "labels": [ "Cell" ] } } ] } ]
{ "text": "We examined bulk TCR repertoires of intestinal CD8 T cells of colonic and small intestinal biopsy samples from three separate studies examining non-CD inflammatory gastrointestinal conditions . There was no signal for enrichment of TRBV28 gene usage in these disease settings (Extended Data Fig. 6f–h ).\nSo...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 51, "end": 58, "text": "T cells", "labels": [ "Cell" ] } } ] } ]
{ "text": "We hypothesized that differences in mucosal CD8 TCR repertoire/phenotype may be mirrored within gut-homing CD8 T cells in the circulation, as seen following gluten challenge . We examined TRBV28 usage by circulating CD8 T cells using flow cytometry (dataset 9). Using TCR sequencing (TCR-seq), we validated ...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 111, "end": 118, "text": "T cells", "labels": [ "Cell" ] } }, { "from_name": "label", ...
{ "text": "Intraepithelial duodenal γδ T cells are increased in CD, although their role is unclear . We analyzed a further dataset of 5,552 sorted intestinal CD8 αβ and γδ T cells (dataset 8; Extended Data Fig. 8 ). Clustering of cell transcriptional states recapitulated the key populations described above (Extended ...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 28, "end": 35, "text": "T cells", "labels": [ "Cell" ] } }, { "from_name": "label", ...
{ "text": "γδ T cells showed overlapping transcriptional profiles with mucosal CD8 αβ T cells, albeit with enrichment within specific clusters (Extended Data Fig. 8d,e ). γδ T cells were most enriched within a natural IEL phenotype cluster and the GZMK /FGFBP2 effector populations, and were also present in the CCL4 e...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 3, "end": 10, "text": "T cells", "labels": [ "Cell" ] } }, { "from_name": "label", ...
{ "text": "We analyzed the TCR repertoire of CD8 T cells in this dataset. The T RM and IL7R clusters showed greatest clonal expansion (Extended Data Fig. 8g ). In all participants with CD, TRBV28-containing clonotypes were more clonally expanded than their non-TRBV28 counterparts. TRBV28 clonotypes were enriched in t...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 38, "end": 45, "text": "T cells", "labels": [ "Cell" ] } } ] } ]
{ "text": "We validated these findings through bulk RNA-seq of sorted intestinal αβ CD8 and γδ T cells from participants with and without CD (dataset 6). Gene-set enrichment analysis of CD8 T cell gene expression in ACD showed upregulation of TCR activation gene sets, and enrichment of cluster marker gene sets from T...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 84, "end": 91, "text": "T cells", "labels": [ "Cell" ] } }, { "from_name": "label", ...
{ "text": "Bulk γδ TCR repertoire sequencing (dataset 7) revealed a skewed TRGV repertoire, with reduced TRGV4 and increased TRGV3 use in ACD (Supplementary Fig. 4a,b ), which persisted after treatment, as previously described . Most TRD CDR3 sequences were private; however, increased sequence sharing was noted betwe...	[]
{ "text": "Samples from adults with TCD (GFD with good symptomatic, serological and histological response) were included in scRNA-seq, bulk RNA-seq and TCR-seq experiments (Supplementary Table 1 ). We hypothesized that cell-type and transcriptional changes would normalize with treatment. However, many biological chan...	[]
{ "text": "Specifically, EC changes including increased TA cell proportions and cycling cells (Extended Data Fig. 1b–e ) and the shift toward progenitor states (Fig. 2f ) persisted despite treatment. EEC changes also persisted. However, absorptive function gene expression within mature enterocytes had predominantly n...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 276, "end": 287, "text": "enterocytes", "labels": [ "Cell" ] } } ] } ]
{ "text": "While T FH -like CD4 T cells and T reg cells returned toward control levels on treatment, the CD8 compartment remained perturbed, with reduced natural IELs and increases in T RM (2) CD8 T cells. However, the T RM (2) population showed reduced activation in TCD (lower IFNG , IL32 and pro-inflammatory marker...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 21, "end": 28, "text": "T cells", "labels": [ "Cell" ] } }, { "from_name": "label", ...
{ "text": "We next analyzed duodenal stromal and endothelial populations in CD (dataset 3; Supplementary Fig. 5a–d ). Annotation of stromal populations based on previous descriptions showed S1, S2 and S3 fibroblasts, as well as myofibroblasts, with S1 fibroblasts most common in the duodenum. The pro-inflammatory S4 p...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 193, "end": 204, "text": "fibroblasts", "labels": [ "Cell" ] } }, { "from_name": "label",...
{ "text": "We next performed spatial transcriptomics on duodenal biopsy samples (dataset 4; Fig. 6 ). Spatial transcriptomics showed 13 transcriptionally distinct regions within the mucosa, representing compartments of the crypt–villus axis (stem cell niche, lower-crypt and mid-crypt regions and villus zones), stroma...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 336, "end": 350, "text": "lamina propria", "labels": [ "Tissue" ] } }, { "from_name": "la...
{ "text": "These immune-rich regions and LAs showed gene expression patterns associated with B cells ( CD19 , MS4A1 (CD20)), plasma cells ( IGHM , IGHA1 , TXNDC5 ) and T cells ( CD3D , CCR7 , CXCL13 ). Signals of cellular proliferation ( MKI67 , REG1A ) were highly localized in specific clusters. In health, cellular ...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 82, "end": 89, "text": "B cells", "labels": [ "Cell" ] } }, { "from_name": "label", ...
{ "text": "In ACD, villus top regions showed increases in interferon-stimulated genes, markers of proliferation, and IL32 (Fig. 6f ), analogous to epithelial scRNA-seq results. TCR genes, tissue-residency markers ( ITGAE , CXCR6 , KLRB1 ), and cytotoxic CD8 markers ( GZMA , KLRD1 , KLRK1 ) were increased in ACD, sugg...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 344, "end": 350, "text": "T cell", "labels": [ "Cell" ] } } ] } ]
{ "text": "We integrated spatial transcriptomics with scRNA-seq data to predict cell-type locations in mucosa (Supplementary Figs. 6e–j and 7 ). In ACD, TA cell signatures expanded from crypt bases to most villus regions, while mature EC signatures were restricted to superficial epithelial layers. In ACD, LAs showed ...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 383, "end": 389, "text": "B cell", "labels": [ "Cell" ] } }, { "from_name": "label", ...
{ "text": "To further study LAs in CD, we performed further spatial transcriptomics experiments on duodenal biopsy samples in participants with and without CD (dataset 5; Fig. 7 and Extended Data Fig. 9a–c ). Analysis of spatial regions recapitulated our description of key transcriptional regions in the duodenal muco...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 303, "end": 309, "text": "mucosa", "labels": [ "Tissue" ] } }, { "from_name": "label", ...
{ "text": "These lamina propria LAs were located adjacent to stem cell niches and muscularis mucosa (Fig. 7g–i ), with enrichment of T FH -like CD4 T cell, T reg cell and B cell gene signatures. Plasma cell signatures were more widely dispersed in immune-rich regions (Fig. 7i–k and Extended Data Fig. 9d,e ). Genes fo...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 160, "end": 166, "text": "B cell", "labels": [ "Cell" ] } }, { "from_name": "label", ...
{ "text": "We examined the expression of chemokines, cytokines and tumor necrosis factor (TNF) superfamily members, as well as receptor–ligand coexpression, within regions in the spatial transcriptomics dataset (Fig. 8a,b and Supplementary Fig. 8 ). Signaling pathway expression was region dependent, indicating highly...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 1112, "end": 1118, "text": "B cell", "labels": [ "Cell" ] } }, { "from_name": "label", ...
{ "text": "Villus tip regions, demonstrated region-specific activation of T cell and immune-related pathways, including increased expression of IL15 , IL18 , IFNG and IL32, and interactions including CXCR6–CXCL16 , CCR9–CCL25 , DPP4–ADA and HLA-E interactions with KLRC2 and KLRD1 (Fig. 8a and Supplementary Fig. 8 ). ...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 63, "end": 69, "text": "T cell", "labels": [ "Cell" ] } }, { "from_name": "label", ...
{ "text": "To understand how genetic susceptibility can drive CD inflammatory responses, we examined putative genome-wide association study (GWAS) candidate gene expression in spatial regions. Villus, telocyte-rich and LA regions showed enriched expression of multiple GWAS candidates (Extended Data Fig. 10a ). Expres...	[]
{ "text": "scRNA-seq data were examined for cell-type-specific expression of CD genetic susceptibility loci. GWAS candidate genes were most prominent in T cell subsets (Extended Data Fig. 10b ), with the highest signal enrichment in cycling CD8 T cells. Specific putative GWAS candidate genes drove these associations ...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 142, "end": 148, "text": "T cell", "labels": [ "Cell" ] } }, { "from_name": "label", ...
{ "text": "Discussion\nSource paper: PMC12133578" }	[]
{ "text": "This multi-omics study provides an integrated single-cell transcriptomic and proteomic assessment of intestinal immune, epithelial and parenchymal cell populations in adult and pediatric CD, contextualized through integration with spatial transcriptomics analysis. Our results show that perturbations of imm...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 315, "end": 330, "text": "epithelial cell", "labels": [ "Cell" ] } }, { "from_name": "lab...
{ "text": "Our understanding of human duodenal lymphoid structures is incomplete . Isolated gut lymphoid structures may act as immune-inductive sites . In CD, it remains unclear where the immune response to gluten is primed, or where subsequent antigen presentation occurs. Both myeloid and B cell lineages have been p...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 280, "end": 286, "text": "B cell", "labels": [ "Cell" ] } }, { "from_name": "label", ...
{ "text": "Several aspects of the mucosal epithelial and immune response remained perturbed despite a GFD. These findings help explain the observation that subtle abnormalities in duodenal biopsy samples remain despite treatment, with reduced villus height/crypt depth ratios on morphometric analysis . Whether this re...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 246, "end": 251, "text": "crypt", "labels": [ "Tissue" ] } } ] } ]
{ "text": "Intestinal tissue-resident CD8 T cell perturbations, including increases in T RM (2) populations, persisted despite GFD treatment. Therefore, this CD8 T RM (2) state may represent a distinct T cell fate, rather than an activated phenotype alone. T RM cells are long-lived memory populations that persist as ...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 31, "end": 37, "text": "T cell", "labels": [ "Cell" ] } }, { "from_name": "label", ...
{ "text": "CD8 T cell populations exhibited changes in TCR repertoire, a finding validated in multiple datasets. These TCR repertoire changes, along with upregulation of TCR signaling gene sets, may indicate that TCR-dependent activation is relevant in CD, involving a separate mechanism to previously described NKG2C/...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 4, "end": 10, "text": "T cell", "labels": [ "Cell" ] } } ] } ]
{ "text": "There is a series of enterocyte transcriptional states in the human small intestine, with absorptive cellular machinery generally limited to mature ECs, consistent with murine studies . The shift to progenitor states in CD may increase CCL25 expression, implicating the CCL25–CCR9 axis in disease. This shif...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 74, "end": 83, "text": "intestine", "labels": [ "Tissue" ] } }, { "from_name": "label", ...
{ "text": "In contrast to the term ‘villus atrophy’, we observe that the CD epithelium is hyperproliferative, and so the loss of villus structures requires additional explanation. Spatial transcriptomics data indicate specific regions responsible for WNT signaling, and we hypothesize that CD inflammation drives morph...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 65, "end": 75, "text": "epithelium", "labels": [ "Tissue" ] } } ] } ]
{ "text": "Integrating single-cell and spatial transcriptomics data, we have dissected the molecular and cellular basis of the histological changes in CD, including villus epithelial changes, crypt hyperplasia and intraepithelial lymphocytosis. This cellular, spatial transcriptomics description builds on the Marsh–Ob...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 514, "end": 521, "text": "B cells", "labels": [ "Cell" ] } }, { "from_name": "label", ...
{ "text": "Methods\nSource paper: PMC12133578" }	[]
{ "text": "Study participants with CD, and HCs, were identified via Oxford University Hospitals NHS Trust CD clinic and endoscopy service (Oxford, UK). Blood and intestinal biopsy samples were taken at endoscopy with informed consent under the Oxford Gastrointestinal Illnesses Biobank study (REC: 21/YH/0206). Study p...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 141, "end": 146, "text": "Blood", "labels": [ "Tissue" ] } } ] } ]
{ "text": "Peripheral blood mononuclear cells were extracted from whole blood or leukocyte cones via density gradient centrifugation. Briefly, peripheral blood was diluted at a 1:1 ratio with Dulbecco’s phosphate buffered saline without calcium or magnesium (PBS) and layered over Lymphoprep (Axis-Shield) before centr...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 11, "end": 16, "text": "blood", "labels": [ "Tissue" ] } }, { "from_name": "label", ...
{ "text": "Intestinal biopsy samples were collected at endoscopy from duodenum. Biopsy samples for intestinal lymphocyte extraction were immediately placed in sterile R10 medium (as above) or MACS Tissue Storage Solution (Miltenyi Biotec) on ice for transportation, before cryopreservation in CryoStor Cs10 (STEMCELL T...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 99, "end": 109, "text": "lymphocyte", "labels": [ "Cell" ] } }, { "from_name": "label", ...
{ "text": "For immune cell isolation from duodenal biopsy samples for scRNA-seq (10x Genomics, dataset 1), biopsy samples were incubated in R10 medium with 1 mg ml Collagenase D (Roche) and 100 mg ml DNase (Thermo Fisher Scientific) for 1 h in a shaking incubator at 37 °C. Biopsy samples were then dissociated by vigo...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 414, "end": 431, "text": "mononuclear cells", "labels": [ "Cell" ] } }, { "from_name": "l...
{ "text": "The method for EC isolation from duodenal biopsy samples for scRNA-seq (10x Genomics, dataset 1) was adapted from ref. . Biopsy samples were washed in wash medium (HPGA, 1 mM EDTA, 1 mM dithiothreitol), then incubated in chelation medium (HPGA, 1 mM EDTA) at 37 °C for 40 min with agitation. The supernatant...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 114, "end": 117, "text": "ref", "labels": [ "Cell" ] } }, { "from_name": "label", ...
{ "text": "For immune cell isolation from duodenal biopsy samples for scRNA-seq and proteomics (BD Rhapsody, dataset 2), samples were thawed, then diluted with warm X-VIVO (Lonza) + 1% AB serum (Sigma-Aldrich). Biopsy samples underwent enzymatic and mechanical digestion using 0.042 mg ml Liberase TL (Roche) and 1 mg ...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 534, "end": 545, "text": "Lymphocytes", "labels": [ "Cell" ] } }, { "from_name": "label",...
{ "text": "Duodenal biopsy samples for flow cytometry were processed as for scRNA-seq of immune cells (see above). Cells were washed with R10 medium before antibody staining and downstream applications.\nSource paper: PMC12133578" }	[]
{ "text": "Duodenal biopsy samples for fluorescence-activated cell sorting (FACS) of IELs for RNA-seq and TCR repertoire sequencing were placed in 10 ml HBSS with 1 mM EDTA and 1 mM dithiothreitol (both Sigma-Aldrich) and placed in a shaking incubator (200 rpm, 37 °C) for 15 min. IELs were strained through a 70-μm fi...	[]
{ "text": "For spatial transcriptomics, single intestinal biopsy samples were embedded in OCT cryo-embedding matrix (Thermo Fisher Scientific) then frozen in isopentane (Sigma-Aldrich) suspended over liquid nitrogen or dry ice, and stored at −80 °C until use.\nSource paper: PMC12133578" }	[]
{ "text": "For surface marker staining, cells were stained in 50 ml of FACS buffer (PBS + 1 mM EDTA + 0.05% BSA) for 30 min at 4 °C. Surface antibodies and clones used are listed in Supplementary Table 3 . Antibodies were purchased from BioLegend, BD Biosciences, Miltenyi Biotec or Thermo Fisher Scientific.\nSource p...	[]
{ "text": "After staining, cells were stored at 4 °C protected from light until data acquisition. Flow cytometry data were acquired on a BD LSR II flow cytometer (BD Biosciences). FACS samples were surface stained as above, with Sytox Green (Thermo Fisher Scientific) used as a viability dye. FACS was performed on an ...	[]
{ "text": "For sorting by FACS for scRNA-seq of intestinal immune populations, cells were stained with EpCam-PE, CD27-BV421 and CD45-APC-Cy7. Live CD45 or CD27 cells were sorted to include all mucosal immune cell populations, including long-lived CD27 plasma cells, which can downregulate surface CD45 expression.\nSou...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 241, "end": 247, "text": "plasma", "labels": [ "Tissue" ] } }, { "from_name": "label", ...
{ "text": "For sorting by FACS for scRNA-seq of intestinal epithelial populations, cells were stained with EpCAM-PE and CD45-AF700, with live EpCAM cells sorted.\nSource paper: PMC12133578" }	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 102, "end": 104, "text": "PE", "labels": [ "Tissue" ] } } ] } ]
{ "text": "For sorting by FACS for bulk RNA-seq or TCR-seq of CD8 IEL populations, cells were stained with CD45-BV785, CD3-BV711, αβTCR-APC, γδTCR-PE, CD4-BV650 and CD8a-AF700, with live CD45 CD3 αβTCR CD8 CD4 cells sorted.\nSource paper: PMC12133578" }	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 136, "end": 138, "text": "PE", "labels": [ "Tissue" ] } } ] } ]
{ "text": "Libraries were generated using 10x Genomics Chromium Single Cell V(D)J Reagents Kits (v1 Chemistry) per the manufacturer’s instructions. Sorted cells suspended in PBS (plus 0.04% BSA) at a concentration of 1,000 cells per microliter were loaded into one lane of a Chromium controller. Library quality and qu...	[]
{ "text": "Sorted CD45 cells were stained with a cocktail of 79 oligonucleotide-conjugated AbSeq antibodies (BD Biosciences, for 45 min at 4 °C. Cells were then washed to remove residual unbound AbSeq antibodies and loaded onto three BD Rhapsody cartridges (BD Biosciences) for single-cell capture. AbSeq antibodies us...	[]
{ "text": "Single-cell capture and cDNA library preparation were performed using the BD Rhapsody Express Single-Cell Analysis System (BD Biosciences), according to the manufacturer’s instructions. Briefly, cDNA was amplified—ten cycles for resting cells and nine cycles for in vitro-stimulated cells—using the Human Im...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 229, "end": 242, "text": "resting cells", "labels": [ "Cell" ] } } ] } ]
{ "text": "The resulting PCR1 products were purified using AMPure XP magnetic beads (Beckman Coulter), and the respective mRNA and AbSeq/Sample Tag products were separated based on size selection, using different bead ratios (0.7× and 1.2×, respectively). The purified mRNA and Sample Tag PCR1 products were further am...	[]
{ "text": "Cryopreserved, OCT-embedded duodenal biopsy samples were stored at −80 °C until use. Before performing the full protocol, a tissue permeabilization optimization was performed (10x Genomics, Visium Spatial Tissue Optimization), which identified 11 min as the optimum permeabilization time.\nSource paper: PMC...	[]
{ "text": "Samples were processed for spatial transcriptomics per the manufacturer’s instructions (10x Genomics, Visium Spatial), with 2 × 10-μm sections cut on a pre-cooled cryostat for each sample onto two 6.5 × 6.5-mm capture areas, each with approximately 5,000 oligonucleotide-barcoded 55-μm-diameter spots. Slide...	[]
{ "text": "Cryopreserved, OCT-embedded duodenal biopsy samples were stored at −80 °C until use. Spatial transcriptomics was performed using the Visium CytAssist (10x Genomics) workflow for fresh-frozen tissue according to the manufacturer’s instructions. Ten-micron sections were cut on a cryostat pre-cooled to −20 °C...	[]
{ "text": "A TRIzol nucleic acid extraction method was used to extract RNA from low numbers of sorted lymphocytes, as previously described , except that phase-lock gel tubes were replaced with standard 1.5 ml microcentrifuge tubes. Briefly, after sorting, cells were centrifuged (500 g , 5 min), resuspended in 1 ml TR...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 91, "end": 102, "text": "lymphocytes", "labels": [ "Cell" ] } }, { "from_name": "label", ...
{ "text": "Bulk RNA-seq was performed using the Smart-seq2 protocol at the Oxford Genomics Centre (University of Oxford). Around 10 ng RNA was used as a template from each sample for library generation. Barcoded samples were pooled, and External RNA Controls Consortium RNA (1:100,000 dilution) was added before 75-bp ...	[]
{ "text": "Bulk TCR repertoire sequencing was performed using the amplicon-rescued multiplex-PCR method (iRepertoire). This method performs an initial first-round RT–PCR with TCR V and C gene-specific primers for the relevant TCR chain, followed by further amplification steps with universal primers for the exponentia...	[]
{ "text": "This was an observational, descriptive study. The experiments were not randomized. No statistical method was used to predetermine sample size, but our sample sizes are similar to those reported in previous publications . No data were excluded from analyses. The investigators were not blinded to allocation ...	[]
{ "text": "All statistical analyses and graphs, except transcriptional data, were performed using Prism Software v9 and v10 (GraphPad). Specific statistical tests are described in relevant figure legends. All data are presented as the mean ± s.e.m. unless stated otherwise. Flow cytometry data were analyzed using Flow...	[]
{ "text": "Raw sequencing read data were subjected to quality control and aligned to the human reference hg38 genome using STAR aligner. The DESeq2 R package was used for downstream differential expression analysis.\nSource paper: PMC12133578" }	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 0, "end": 3, "text": "Raw", "labels": [ "Cell" ] } } ] } ]
{ "text": "Bulk TCR repertoire analysis was performed using the iRepertoire analysis pipeline.\nSource paper: PMC12133578" }	[]
{ "text": "Raw read data were processed with either the Cell Ranger pipeline or the BD Genomics pipeline. Downstream analyses were carried out in R using the Seurat pipeline.\nSource paper: PMC12133578" }	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 0, "end": 3, "text": "Raw", "labels": [ "Cell" ] } } ] } ]
{ "text": "Raw read data were processed using the Space Ranger pipeline. Downstream analyses were carried out in R using the Seurat pipeline.\nSource paper: PMC12133578" }	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 0, "end": 3, "text": "Raw", "labels": [ "Cell" ] } } ] } ]
{ "text": "Raw sequencing read data were processed with the Cell Ranger VDJ pipeline. Downstream analyses were carried out in R.\nSource paper: PMC12133578" }	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 0, "end": 3, "text": "Raw", "labels": [ "Cell" ] } } ] } ]
{ "text": "Additional details for computational data analysis are provided in Supplementary Methods .\nSource paper: PMC12133578" }	[]
{ "text": "Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article.\nSource paper: PMC12133578" }	[]
{ "text": "Online content\nSource paper: PMC12133578" }	[]
{ "text": "Any methods, additional references, Nature Portfolio reporting summaries, source data, extended data, supplementary information, acknowledgements, peer review information; details of author contributions and competing interests; and statements of data and code availability are available at 10.1038/s41590-0...	[]
{ "text": "PMC12256823\nSource paper: PMC12256823" }	[]
{ "text": "Bi-allelic variants in POPDC2 cause an autosomal recessive syndrome presenting with cardiac conduction defects and hypertrophic cardiomyopathy\nSource paper: PMC12256823" }	[]
{ "text": "Abstract\nSource paper: PMC12256823" }	[]
{ "text": "POPDC2 encodes the Popeye domain-containing protein 2, which has an important role in cardiac pacemaking and conduction, due in part to its cyclic AMP (cAMP)-dependent binding and regulation of TREK-1 potassium channels. Loss of Popdc2 in mice results in sinus pauses and bradycardia, and morpholino-mediate...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 1197, "end": 1203, "text": "hearts", "labels": [ "Tissue" ] } }, { "from_name": "label", ...
{ "text": "Introduction\nSource paper: PMC12256823" }	[]
{ "text": "The rhythmic contraction of the heart is orchestrated by the cardiac pacemaker and conduction system. Electrical activity in the heart arises in the sinus node, located in the right atrium near the entrance of the superior vena cava. The electrical impulse then spreads through the atria to the atrioventric...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 32, "end": 37, "text": "heart", "labels": [ "Tissue" ] } }, { "from_name": "label", ...
{ "text": "Cardiac conduction defects (CCDs; MIM: 115080 ) are primarily the consequence of age-related degeneration, structural heart disease, or post-operative complications. Presentation of CCDs in the young should raise suspicion of a genetic disorder. Rare variants in genes encoding cardiac ion channels (e.g., S...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 118, "end": 123, "text": "heart", "labels": [ "Tissue" ] } } ] } ]
{ "text": "Bi-allelic variants in POPDC1 (also known as BVES , MIM: 604577 ), encoding the Popeye domain-containing protein 1, are associated with muscular dystrophy and AV block (MIM: 604577 ). In mice, knockout of Popdc1 or Popdc2 resulted in stress-induced sinus pauses and sinus bradycardia. In zebrafish, morpholi...	[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 878, "end": 882, "text": "node", "labels": [ "Tissue" ] } } ] } ]

{ "text": "We generated scRNA-seq profiles of duodenal epithelial, immune and parenchymal populations from 35 participants: 21 with CD (16 children, 5 adults) and 14 controls (5 children, 9 adults; Fig. 1 and Supplementary Table 1 ). We used complementary single-cell techniques for adult and pediatric datasets, with ...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 461, "end": 478, "text": "endothelial cells", "labels": [ "Cell" ] } } ] } ]

{ "text": "We analyzed EPCAM epithelial populations from dataset 1. Nine transcriptionally distinct epithelial cell (EC) clusters were identified, representing progenitor, secretory and absorptive lineages along the developmental progression of the crypt–villus axis (Fig. 2a,b , Extended Data Fig. 1a and Supplementar...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 89, "end": 104, "text": "epithelial cell", "labels": [ "Cell" ] } }, { "from_name": "labe...

{ "text": "A LYZ Paneth cell-like population ( MMP7 REG1A SOD3 PLA2G2A ) was also identified (Fig. 2a,b ), although defensin gene expression was not detected. This population expressed PGC , mucins including MUC5AC , MUC1 and MUC6 and AQP5 , suggesting it also contained Brunner’s gland cells or ectopic gastric pylori...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 270, "end": 275, "text": "gland", "labels": [ "Tissue" ] } }, { "from_name": "label", ...

{ "text": "Transit-amplifying (TA) cells were increased in CD, along with enrichment of uniform manifold approximation and projection (UMAP) areas corresponding to EC progenitors (stem cells, TA cells and early enterocytes; Fig. 2c,d ). This persisted in treated celiac disease (TCD; Extended Data Fig. 1b,c ). In para...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 169, "end": 173, "text": "stem", "labels": [ "Tissue" ] } }, { "from_name": "label", ...

{ "text": "Pseudotime analyses identified epithelial developmental trajectories, from undifferentiated progenitor states toward absorptive and secretory lineages (Fig. 2e ). In CD, ECs were shifted to earlier pseudotime states, with loss of mature ECs (Fig. 2f ). CCL25 , encoding the ligand for CCR9 (implicated in CD...

[]

{ "text": "We examined putative EC functions through functional gene-set analysis (Extended Data Fig. 1a ), identifying functions of secretory Paneth-like/Brunner’s gland cells (secreted protein and vesicle pathways), BEST4 enterocytes (chloride/anion channel activity), tuft cells (taste perception) and enteroendocri...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 625, "end": 635, "text": "epithelium", "labels": [ "Tissue" ] } }, { "from_name": "label"...

{ "text": "ECs in ACD upregulated multiple antigen-presentation molecules, including classical HLA class I and class II genes (except HLA-DQ ) and nonclassical genes including HLA-E and HLA-F (Fig. 2h ). Interferon-stimulated genes (types I and II) dominated the epithelial response, including STAT1 (Fig. 2h and Suppl...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 500, "end": 510, "text": "lymphocyte", "labels": [ "Cell" ] } } ] } ]

{ "text": "Some transcriptional changes were cell-type specific. IL32 was highly expressed in ACD by mature enterocytes (Extended Data Fig. 1k ), perhaps regulated by interferons. The reduction of fatty acid catabolism/transport ( APOA1 , FABP2 ), metal ion transport (iron: FTH1 , FTL ; zinc: SLC39A4 ) and carbohydra...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 665, "end": 668, "text": "gut", "labels": [ "Tissue" ] } }, { "from_name": "label", ...

{ "text": "The duodenum, where CD inflammation predominates, has sensory and neurohormonal functions. We extended EEC clustering, revealing multiple transcriptional states, including NEUROG3 progenitors and EEC subtypes, which showed similar CD-related transcriptional changes to other ECs (Extended Data Fig. 2 ). EEC...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 4, "end": 12, "text": "duodenum", "labels": [ "Tissue" ] } }, { "from_name": "label", ...

{ "text": "In adults (dataset 1), CD4 T cells formed subsets dominated by T H 1-polarized and IL-17-producing helper T (T H 17)-polarized effectors, as well as small naive and FOXP3 regulatory populations (Fig. 3a–c and Supplementary Table 6 ). There was a cluster of T FH -like CD4 T cells expressing PDCD1 , BTLA , C...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 27, "end": 34, "text": "T cells", "labels": [ "Cell" ] } }, { "from_name": "label", ...

{ "text": "This T FH -like population in adults and children showed similar phenotypic profiles to those of gut-resident gluten-specific CD4 T cells in CD (Extended Data Fig. 3b ), and expressed TOX2 , CD200 , IL21 and CXCL13 . The cluster showed enrichment of TRBV7-2 , a V-gene enriched in gluten-specific CD4 T cell...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 130, "end": 137, "text": "T cells", "labels": [ "Cell" ] } }, { "from_name": "label", ...

{ "text": "T cell populations showed distinct cytokine and chemokine expression patterns (Extended Data Fig. 3c ). The CD-associated T FH -like population, showed high CXCL13 and IL21 expression, with IFNG and IL21 coexpression (Fig. 3j,k ), similarly to gluten-specific T cells . T FH -like cells expressed TNFSF8 , C...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 0, "end": 6, "text": "T cell", "labels": [ "Cell" ] } }, { "from_name": "label", ...

{ "text": "Oral gluten challenge in CD drives rapid circulating cytokine responses, including IL-2, CXCL8, CXCL10 and IL-6 (ref. ). CXCL8 expression was highest in CCR7 T FH CD4 T cells, CXCL10 was detected in T FH -like CD4 T cells, while IL6 was detected in T reg cells (Extended Data Fig. 3c ). IL2 expression was l...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 113, "end": 116, "text": "ref", "labels": [ "Cell" ] } }, { "from_name": "label", ...

{ "text": "We examined transcription factor (TF), and regulon expression within CD4 subsets, with canonical TFs and regulons of T H 17 and T reg cell function expressed as expected (Extended Data Fig. 3e–g ). IKZF1 and its regulon were upregulated in T FH -like cells, with intermediate expression of RUNX1 , BATF and ...

[]

{ "text": "We examined B cell lineages in dataset 2 (pediatric; Extended Data Fig. 4a,b ). Both IgA and IgM plasma cells were increased in CD (Extended Data Fig. 4c–f ). A population of CXCR5 B cells ( MS4A1 CD19 CD20 ) were present, with a shift toward the CD27 memory B cell phenotype in CD.\nSource paper: PMC121335...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 12, "end": 18, "text": "B cell", "labels": [ "Cell" ] } }, { "from_name": "label", ...

{ "text": "Gene signatures of age-related B cells (an inflammation-associated population in autoimmune disease ), including ITGAM , ITGAX , CD86 and BATF , were expressed most highly in CD27 B cell populations, while a key age-related B cell TF, TBX21 , was highly expressed in cycling B cells (Extended Data Fig. 4b )...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 31, "end": 38, "text": "B cells", "labels": [ "Cell" ] } }, { "from_name": "label", ...

{ "text": "Intestinal myeloid cell populations are impacted by CD and may be involved in antigen presentation and oral tolerance . Myeloid cells (dataset 2) formed 11 transcriptionally distinct clusters, including macrophages, conventional dendritic cells and plasmacytoid dendritic cells (Supplementary Fig. 2a–c ). H...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 203, "end": 214, "text": "macrophages", "labels": [ "Cell" ] } }, { "from_name": "label",...

{ "text": "Intestinal CD8 T cells showed considerable heterogeneity in transcriptional states, with multiple tissue-resident memory CD8 T (T RM ) cells, including an ITGAE IL7R population, a CCL4 CD69 ITGAE population and two subsets of ITGAE T RM cells (Fig. 4 , Extended Data Fig. 5a and Supplementary Table 7 ). The...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 15, "end": 22, "text": "T cells", "labels": [ "Cell" ] } }, { "from_name": "label", ...

{ "text": "We analyzed subsets relevant to CD, including natural killer (NK)-receptor expressing IELs and killer-cell immunoglobulin-like receptor (KIR)-positive CD8 T cells . KLRC1 (NKG2A) was expressed by CCL4 cells, while KLRC2 (NKG2C) was expressed by resident IL7R , T RM (1) and T RM (2) subsets (Extended Data F...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 155, "end": 162, "text": "T cells", "labels": [ "Cell" ] } } ] } ]

{ "text": "T RM (2) and cycling populations were enriched in ACD, but not T RM (1) cells (Fig. 4f,g ). T RM (2) cells were rare in health, but increased to form 20–40% of CD8 T cells in ACD, which persisted in TCD (Fig. 4h ). Natural IELs were reduced in ACD (Extended Data Fig. 5e ). Cycling CD8 T cells increased to ...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 164, "end": 171, "text": "T cells", "labels": [ "Cell" ] } }, { "from_name": "label", ...

{ "text": "As T RM (2) CD8 T cells were increased in proportion and proliferating in ACD, we profiled them in depth (Fig. 5a–e and Extended Data Fig. 6 ). T RM (2) CD8 T cells showed a CD103 tissue-resident phenotype, high GZMA and absent GZMK expression, along with high expression of CXCR6, activation markers ( HLA-...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 16, "end": 23, "text": "T cells", "labels": [ "Cell" ] } }, { "from_name": "label", ...

{ "text": "We examined pseudotime trajectories of tissue-resident clusters with TCR repertoire clonal sharing (T RM (1), T RM (2), IL7R and CCL4 effectors) to infer putative differentiation pathways (Fig. 5a,b,e ). The pseudotime trajectory showed two branches, formed predominantly of T RM (1) cells in branch 1 and T...

[]

{ "text": "We examined cytokine, chemokine and TF expression by CD8 T cell subsets. The predominant CD8 sources of IFNG were CD8 T RM (2) and cycling clusters (Fig. 5c,d and Extended Data Fig. 5g–i ). These populations also expressed the chemokine CCL5 , CD70 and FASLG . Natural IELs (reduced in ACD), produced CCL2 ,...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 57, "end": 63, "text": "T cell", "labels": [ "Cell" ] } } ] } ]

{ "text": "CD8 T cell-induced epithelial damage is thought to be mediated via TCR-independent mechanisms. We hypothesized that CD8 T cell TCR repertoires would be similar in health and disease. Single-cell TCR sequences were examined, which showed expected clonal overlap between tissue-resident populations (Fig. 5e a...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 4, "end": 10, "text": "T cell", "labels": [ "Cell" ] } }, { "from_name": "label", ...

{ "text": "Consequently, we sorted intraepithelial CD8 T cells from 12 adults with and without CD (dataset 3) and performed bulk RNA-seq. This showed significant enrichment of one TRBV segment, TRBV28 , enriched in ACD and TCD, but not controls (Fig. 5g ). TRBV28 was the high-frequency V segment with the highest fold...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 44, "end": 51, "text": "T cells", "labels": [ "Cell" ] } } ] } ]

{ "text": "We validated this by performing bulk TCR repertoire sequencing on 1,068,814 mucosal CD8 T cells from 20 donors with and without CD (dataset 4). Again, TRBV28 was highly upregulated in CD, forming 10% of unique CDR3 sequences in ACD and TCD, versus 2% in controls (Fig. 5h ). TRBV28 was also enriched within ...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 88, "end": 95, "text": "T cells", "labels": [ "Cell" ] } } ] } ]

{ "text": "We examined bulk TCR repertoires of intestinal CD8 T cells of colonic and small intestinal biopsy samples from three separate studies examining non-CD inflammatory gastrointestinal conditions . There was no signal for enrichment of TRBV28 gene usage in these disease settings (Extended Data Fig. 6f–h ).\nSo...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 51, "end": 58, "text": "T cells", "labels": [ "Cell" ] } } ] } ]

{ "text": "We hypothesized that differences in mucosal CD8 TCR repertoire/phenotype may be mirrored within gut-homing CD8 T cells in the circulation, as seen following gluten challenge . We examined TRBV28 usage by circulating CD8 T cells using flow cytometry (dataset 9). Using TCR sequencing (TCR-seq), we validated ...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 111, "end": 118, "text": "T cells", "labels": [ "Cell" ] } }, { "from_name": "label", ...

{ "text": "Intraepithelial duodenal γδ T cells are increased in CD, although their role is unclear . We analyzed a further dataset of 5,552 sorted intestinal CD8 αβ and γδ T cells (dataset 8; Extended Data Fig. 8 ). Clustering of cell transcriptional states recapitulated the key populations described above (Extended ...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 28, "end": 35, "text": "T cells", "labels": [ "Cell" ] } }, { "from_name": "label", ...

{ "text": "γδ T cells showed overlapping transcriptional profiles with mucosal CD8 αβ T cells, albeit with enrichment within specific clusters (Extended Data Fig. 8d,e ). γδ T cells were most enriched within a natural IEL phenotype cluster and the GZMK /FGFBP2 effector populations, and were also present in the CCL4 e...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 3, "end": 10, "text": "T cells", "labels": [ "Cell" ] } }, { "from_name": "label", ...

{ "text": "We analyzed the TCR repertoire of CD8 T cells in this dataset. The T RM and IL7R clusters showed greatest clonal expansion (Extended Data Fig. 8g ). In all participants with CD, TRBV28-containing clonotypes were more clonally expanded than their non-TRBV28 counterparts. TRBV28 clonotypes were enriched in t...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 38, "end": 45, "text": "T cells", "labels": [ "Cell" ] } } ] } ]

{ "text": "We validated these findings through bulk RNA-seq of sorted intestinal αβ CD8 and γδ T cells from participants with and without CD (dataset 6). Gene-set enrichment analysis of CD8 T cell gene expression in ACD showed upregulation of TCR activation gene sets, and enrichment of cluster marker gene sets from T...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 84, "end": 91, "text": "T cells", "labels": [ "Cell" ] } }, { "from_name": "label", ...

{ "text": "Bulk γδ TCR repertoire sequencing (dataset 7) revealed a skewed TRGV repertoire, with reduced TRGV4 and increased TRGV3 use in ACD (Supplementary Fig. 4a,b ), which persisted after treatment, as previously described . Most TRD CDR3 sequences were private; however, increased sequence sharing was noted betwe...

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{ "text": "Samples from adults with TCD (GFD with good symptomatic, serological and histological response) were included in scRNA-seq, bulk RNA-seq and TCR-seq experiments (Supplementary Table 1 ). We hypothesized that cell-type and transcriptional changes would normalize with treatment. However, many biological chan...

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{ "text": "Specifically, EC changes including increased TA cell proportions and cycling cells (Extended Data Fig. 1b–e ) and the shift toward progenitor states (Fig. 2f ) persisted despite treatment. EEC changes also persisted. However, absorptive function gene expression within mature enterocytes had predominantly n...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 276, "end": 287, "text": "enterocytes", "labels": [ "Cell" ] } } ] } ]

{ "text": "While T FH -like CD4 T cells and T reg cells returned toward control levels on treatment, the CD8 compartment remained perturbed, with reduced natural IELs and increases in T RM (2) CD8 T cells. However, the T RM (2) population showed reduced activation in TCD (lower IFNG , IL32 and pro-inflammatory marker...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 21, "end": 28, "text": "T cells", "labels": [ "Cell" ] } }, { "from_name": "label", ...

{ "text": "We next analyzed duodenal stromal and endothelial populations in CD (dataset 3; Supplementary Fig. 5a–d ). Annotation of stromal populations based on previous descriptions showed S1, S2 and S3 fibroblasts, as well as myofibroblasts, with S1 fibroblasts most common in the duodenum. The pro-inflammatory S4 p...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 193, "end": 204, "text": "fibroblasts", "labels": [ "Cell" ] } }, { "from_name": "label",...

{ "text": "We next performed spatial transcriptomics on duodenal biopsy samples (dataset 4; Fig. 6 ). Spatial transcriptomics showed 13 transcriptionally distinct regions within the mucosa, representing compartments of the crypt–villus axis (stem cell niche, lower-crypt and mid-crypt regions and villus zones), stroma...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 336, "end": 350, "text": "lamina propria", "labels": [ "Tissue" ] } }, { "from_name": "la...

{ "text": "These immune-rich regions and LAs showed gene expression patterns associated with B cells ( CD19 , MS4A1 (CD20)), plasma cells ( IGHM , IGHA1 , TXNDC5 ) and T cells ( CD3D , CCR7 , CXCL13 ). Signals of cellular proliferation ( MKI67 , REG1A ) were highly localized in specific clusters. In health, cellular ...

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{ "text": "In ACD, villus top regions showed increases in interferon-stimulated genes, markers of proliferation, and IL32 (Fig. 6f ), analogous to epithelial scRNA-seq results. TCR genes, tissue-residency markers ( ITGAE , CXCR6 , KLRB1 ), and cytotoxic CD8 markers ( GZMA , KLRD1 , KLRK1 ) were increased in ACD, sugg...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 344, "end": 350, "text": "T cell", "labels": [ "Cell" ] } } ] } ]

{ "text": "We integrated spatial transcriptomics with scRNA-seq data to predict cell-type locations in mucosa (Supplementary Figs. 6e–j and 7 ). In ACD, TA cell signatures expanded from crypt bases to most villus regions, while mature EC signatures were restricted to superficial epithelial layers. In ACD, LAs showed ...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 383, "end": 389, "text": "B cell", "labels": [ "Cell" ] } }, { "from_name": "label", ...

{ "text": "To further study LAs in CD, we performed further spatial transcriptomics experiments on duodenal biopsy samples in participants with and without CD (dataset 5; Fig. 7 and Extended Data Fig. 9a–c ). Analysis of spatial regions recapitulated our description of key transcriptional regions in the duodenal muco...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 303, "end": 309, "text": "mucosa", "labels": [ "Tissue" ] } }, { "from_name": "label", ...

{ "text": "These lamina propria LAs were located adjacent to stem cell niches and muscularis mucosa (Fig. 7g–i ), with enrichment of T FH -like CD4 T cell, T reg cell and B cell gene signatures. Plasma cell signatures were more widely dispersed in immune-rich regions (Fig. 7i–k and Extended Data Fig. 9d,e ). Genes fo...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 160, "end": 166, "text": "B cell", "labels": [ "Cell" ] } }, { "from_name": "label", ...

{ "text": "We examined the expression of chemokines, cytokines and tumor necrosis factor (TNF) superfamily members, as well as receptor–ligand coexpression, within regions in the spatial transcriptomics dataset (Fig. 8a,b and Supplementary Fig. 8 ). Signaling pathway expression was region dependent, indicating highly...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 1112, "end": 1118, "text": "B cell", "labels": [ "Cell" ] } }, { "from_name": "label", ...

{ "text": "Villus tip regions, demonstrated region-specific activation of T cell and immune-related pathways, including increased expression of IL15 , IL18 , IFNG and IL32, and interactions including CXCR6–CXCL16 , CCR9–CCL25 , DPP4–ADA and HLA-E interactions with KLRC2 and KLRD1 (Fig. 8a and Supplementary Fig. 8 ). ...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 63, "end": 69, "text": "T cell", "labels": [ "Cell" ] } }, { "from_name": "label", ...

{ "text": "To understand how genetic susceptibility can drive CD inflammatory responses, we examined putative genome-wide association study (GWAS) candidate gene expression in spatial regions. Villus, telocyte-rich and LA regions showed enriched expression of multiple GWAS candidates (Extended Data Fig. 10a ). Expres...

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{ "text": "scRNA-seq data were examined for cell-type-specific expression of CD genetic susceptibility loci. GWAS candidate genes were most prominent in T cell subsets (Extended Data Fig. 10b ), with the highest signal enrichment in cycling CD8 T cells. Specific putative GWAS candidate genes drove these associations ...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 142, "end": 148, "text": "T cell", "labels": [ "Cell" ] } }, { "from_name": "label", ...

{ "text": "Discussion\nSource paper: PMC12133578" }

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{ "text": "This multi-omics study provides an integrated single-cell transcriptomic and proteomic assessment of intestinal immune, epithelial and parenchymal cell populations in adult and pediatric CD, contextualized through integration with spatial transcriptomics analysis. Our results show that perturbations of imm...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 315, "end": 330, "text": "epithelial cell", "labels": [ "Cell" ] } }, { "from_name": "lab...

{ "text": "Our understanding of human duodenal lymphoid structures is incomplete . Isolated gut lymphoid structures may act as immune-inductive sites . In CD, it remains unclear where the immune response to gluten is primed, or where subsequent antigen presentation occurs. Both myeloid and B cell lineages have been p...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 280, "end": 286, "text": "B cell", "labels": [ "Cell" ] } }, { "from_name": "label", ...

{ "text": "Several aspects of the mucosal epithelial and immune response remained perturbed despite a GFD. These findings help explain the observation that subtle abnormalities in duodenal biopsy samples remain despite treatment, with reduced villus height/crypt depth ratios on morphometric analysis . Whether this re...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 246, "end": 251, "text": "crypt", "labels": [ "Tissue" ] } } ] } ]

{ "text": "Intestinal tissue-resident CD8 T cell perturbations, including increases in T RM (2) populations, persisted despite GFD treatment. Therefore, this CD8 T RM (2) state may represent a distinct T cell fate, rather than an activated phenotype alone. T RM cells are long-lived memory populations that persist as ...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 31, "end": 37, "text": "T cell", "labels": [ "Cell" ] } }, { "from_name": "label", ...

{ "text": "CD8 T cell populations exhibited changes in TCR repertoire, a finding validated in multiple datasets. These TCR repertoire changes, along with upregulation of TCR signaling gene sets, may indicate that TCR-dependent activation is relevant in CD, involving a separate mechanism to previously described NKG2C/...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 4, "end": 10, "text": "T cell", "labels": [ "Cell" ] } } ] } ]

{ "text": "There is a series of enterocyte transcriptional states in the human small intestine, with absorptive cellular machinery generally limited to mature ECs, consistent with murine studies . The shift to progenitor states in CD may increase CCL25 expression, implicating the CCL25–CCR9 axis in disease. This shif...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 74, "end": 83, "text": "intestine", "labels": [ "Tissue" ] } }, { "from_name": "label", ...

{ "text": "In contrast to the term ‘villus atrophy’, we observe that the CD epithelium is hyperproliferative, and so the loss of villus structures requires additional explanation. Spatial transcriptomics data indicate specific regions responsible for WNT signaling, and we hypothesize that CD inflammation drives morph...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 65, "end": 75, "text": "epithelium", "labels": [ "Tissue" ] } } ] } ]

{ "text": "Integrating single-cell and spatial transcriptomics data, we have dissected the molecular and cellular basis of the histological changes in CD, including villus epithelial changes, crypt hyperplasia and intraepithelial lymphocytosis. This cellular, spatial transcriptomics description builds on the Marsh–Ob...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 514, "end": 521, "text": "B cells", "labels": [ "Cell" ] } }, { "from_name": "label", ...

{ "text": "Methods\nSource paper: PMC12133578" }

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{ "text": "Study participants with CD, and HCs, were identified via Oxford University Hospitals NHS Trust CD clinic and endoscopy service (Oxford, UK). Blood and intestinal biopsy samples were taken at endoscopy with informed consent under the Oxford Gastrointestinal Illnesses Biobank study (REC: 21/YH/0206). Study p...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 141, "end": 146, "text": "Blood", "labels": [ "Tissue" ] } } ] } ]

{ "text": "Peripheral blood mononuclear cells were extracted from whole blood or leukocyte cones via density gradient centrifugation. Briefly, peripheral blood was diluted at a 1:1 ratio with Dulbecco’s phosphate buffered saline without calcium or magnesium (PBS) and layered over Lymphoprep (Axis-Shield) before centr...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 11, "end": 16, "text": "blood", "labels": [ "Tissue" ] } }, { "from_name": "label", ...

{ "text": "Intestinal biopsy samples were collected at endoscopy from duodenum. Biopsy samples for intestinal lymphocyte extraction were immediately placed in sterile R10 medium (as above) or MACS Tissue Storage Solution (Miltenyi Biotec) on ice for transportation, before cryopreservation in CryoStor Cs10 (STEMCELL T...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 99, "end": 109, "text": "lymphocyte", "labels": [ "Cell" ] } }, { "from_name": "label", ...

{ "text": "For immune cell isolation from duodenal biopsy samples for scRNA-seq (10x Genomics, dataset 1), biopsy samples were incubated in R10 medium with 1 mg ml Collagenase D (Roche) and 100 mg ml DNase (Thermo Fisher Scientific) for 1 h in a shaking incubator at 37 °C. Biopsy samples were then dissociated by vigo...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 414, "end": 431, "text": "mononuclear cells", "labels": [ "Cell" ] } }, { "from_name": "l...

{ "text": "The method for EC isolation from duodenal biopsy samples for scRNA-seq (10x Genomics, dataset 1) was adapted from ref. . Biopsy samples were washed in wash medium (HPGA, 1 mM EDTA, 1 mM dithiothreitol), then incubated in chelation medium (HPGA, 1 mM EDTA) at 37 °C for 40 min with agitation. The supernatant...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 114, "end": 117, "text": "ref", "labels": [ "Cell" ] } }, { "from_name": "label", ...

{ "text": "For immune cell isolation from duodenal biopsy samples for scRNA-seq and proteomics (BD Rhapsody, dataset 2), samples were thawed, then diluted with warm X-VIVO (Lonza) + 1% AB serum (Sigma-Aldrich). Biopsy samples underwent enzymatic and mechanical digestion using 0.042 mg ml Liberase TL (Roche) and 1 mg ...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 534, "end": 545, "text": "Lymphocytes", "labels": [ "Cell" ] } }, { "from_name": "label",...

{ "text": "Duodenal biopsy samples for flow cytometry were processed as for scRNA-seq of immune cells (see above). Cells were washed with R10 medium before antibody staining and downstream applications.\nSource paper: PMC12133578" }

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{ "text": "Duodenal biopsy samples for fluorescence-activated cell sorting (FACS) of IELs for RNA-seq and TCR repertoire sequencing were placed in 10 ml HBSS with 1 mM EDTA and 1 mM dithiothreitol (both Sigma-Aldrich) and placed in a shaking incubator (200 rpm, 37 °C) for 15 min. IELs were strained through a 70-μm fi...

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{ "text": "For spatial transcriptomics, single intestinal biopsy samples were embedded in OCT cryo-embedding matrix (Thermo Fisher Scientific) then frozen in isopentane (Sigma-Aldrich) suspended over liquid nitrogen or dry ice, and stored at −80 °C until use.\nSource paper: PMC12133578" }

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{ "text": "For surface marker staining, cells were stained in 50 ml of FACS buffer (PBS + 1 mM EDTA + 0.05% BSA) for 30 min at 4 °C. Surface antibodies and clones used are listed in Supplementary Table 3 . Antibodies were purchased from BioLegend, BD Biosciences, Miltenyi Biotec or Thermo Fisher Scientific.\nSource p...

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{ "text": "After staining, cells were stored at 4 °C protected from light until data acquisition. Flow cytometry data were acquired on a BD LSR II flow cytometer (BD Biosciences). FACS samples were surface stained as above, with Sytox Green (Thermo Fisher Scientific) used as a viability dye. FACS was performed on an ...

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{ "text": "For sorting by FACS for scRNA-seq of intestinal immune populations, cells were stained with EpCam-PE, CD27-BV421 and CD45-APC-Cy7. Live CD45 or CD27 cells were sorted to include all mucosal immune cell populations, including long-lived CD27 plasma cells, which can downregulate surface CD45 expression.\nSou...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 241, "end": 247, "text": "plasma", "labels": [ "Tissue" ] } }, { "from_name": "label", ...

{ "text": "For sorting by FACS for scRNA-seq of intestinal epithelial populations, cells were stained with EpCAM-PE and CD45-AF700, with live EpCAM cells sorted.\nSource paper: PMC12133578" }

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 102, "end": 104, "text": "PE", "labels": [ "Tissue" ] } } ] } ]

{ "text": "For sorting by FACS for bulk RNA-seq or TCR-seq of CD8 IEL populations, cells were stained with CD45-BV785, CD3-BV711, αβTCR-APC, γδTCR-PE, CD4-BV650 and CD8a-AF700, with live CD45 CD3 αβTCR CD8 CD4 cells sorted.\nSource paper: PMC12133578" }

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 136, "end": 138, "text": "PE", "labels": [ "Tissue" ] } } ] } ]

{ "text": "Libraries were generated using 10x Genomics Chromium Single Cell V(D)J Reagents Kits (v1 Chemistry) per the manufacturer’s instructions. Sorted cells suspended in PBS (plus 0.04% BSA) at a concentration of 1,000 cells per microliter were loaded into one lane of a Chromium controller. Library quality and qu...

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{ "text": "Sorted CD45 cells were stained with a cocktail of 79 oligonucleotide-conjugated AbSeq antibodies (BD Biosciences, for 45 min at 4 °C. Cells were then washed to remove residual unbound AbSeq antibodies and loaded onto three BD Rhapsody cartridges (BD Biosciences) for single-cell capture. AbSeq antibodies us...

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{ "text": "Single-cell capture and cDNA library preparation were performed using the BD Rhapsody Express Single-Cell Analysis System (BD Biosciences), according to the manufacturer’s instructions. Briefly, cDNA was amplified—ten cycles for resting cells and nine cycles for in vitro-stimulated cells—using the Human Im...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 229, "end": 242, "text": "resting cells", "labels": [ "Cell" ] } } ] } ]

{ "text": "The resulting PCR1 products were purified using AMPure XP magnetic beads (Beckman Coulter), and the respective mRNA and AbSeq/Sample Tag products were separated based on size selection, using different bead ratios (0.7× and 1.2×, respectively). The purified mRNA and Sample Tag PCR1 products were further am...

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{ "text": "Cryopreserved, OCT-embedded duodenal biopsy samples were stored at −80 °C until use. Before performing the full protocol, a tissue permeabilization optimization was performed (10x Genomics, Visium Spatial Tissue Optimization), which identified 11 min as the optimum permeabilization time.\nSource paper: PMC...

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{ "text": "Samples were processed for spatial transcriptomics per the manufacturer’s instructions (10x Genomics, Visium Spatial), with 2 × 10-μm sections cut on a pre-cooled cryostat for each sample onto two 6.5 × 6.5-mm capture areas, each with approximately 5,000 oligonucleotide-barcoded 55-μm-diameter spots. Slide...

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{ "text": "Cryopreserved, OCT-embedded duodenal biopsy samples were stored at −80 °C until use. Spatial transcriptomics was performed using the Visium CytAssist (10x Genomics) workflow for fresh-frozen tissue according to the manufacturer’s instructions. Ten-micron sections were cut on a cryostat pre-cooled to −20 °C...

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{ "text": "A TRIzol nucleic acid extraction method was used to extract RNA from low numbers of sorted lymphocytes, as previously described , except that phase-lock gel tubes were replaced with standard 1.5 ml microcentrifuge tubes. Briefly, after sorting, cells were centrifuged (500 g , 5 min), resuspended in 1 ml TR...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 91, "end": 102, "text": "lymphocytes", "labels": [ "Cell" ] } }, { "from_name": "label", ...

{ "text": "Bulk RNA-seq was performed using the Smart-seq2 protocol at the Oxford Genomics Centre (University of Oxford). Around 10 ng RNA was used as a template from each sample for library generation. Barcoded samples were pooled, and External RNA Controls Consortium RNA (1:100,000 dilution) was added before 75-bp ...

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{ "text": "Bulk TCR repertoire sequencing was performed using the amplicon-rescued multiplex-PCR method (iRepertoire). This method performs an initial first-round RT–PCR with TCR V and C gene-specific primers for the relevant TCR chain, followed by further amplification steps with universal primers for the exponentia...

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{ "text": "This was an observational, descriptive study. The experiments were not randomized. No statistical method was used to predetermine sample size, but our sample sizes are similar to those reported in previous publications . No data were excluded from analyses. The investigators were not blinded to allocation ...

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{ "text": "All statistical analyses and graphs, except transcriptional data, were performed using Prism Software v9 and v10 (GraphPad). Specific statistical tests are described in relevant figure legends. All data are presented as the mean ± s.e.m. unless stated otherwise. Flow cytometry data were analyzed using Flow...

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{ "text": "Raw sequencing read data were subjected to quality control and aligned to the human reference hg38 genome using STAR aligner. The DESeq2 R package was used for downstream differential expression analysis.\nSource paper: PMC12133578" }

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 0, "end": 3, "text": "Raw", "labels": [ "Cell" ] } } ] } ]

{ "text": "Bulk TCR repertoire analysis was performed using the iRepertoire analysis pipeline.\nSource paper: PMC12133578" }

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{ "text": "Raw read data were processed with either the Cell Ranger pipeline or the BD Genomics pipeline. Downstream analyses were carried out in R using the Seurat pipeline.\nSource paper: PMC12133578" }

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 0, "end": 3, "text": "Raw", "labels": [ "Cell" ] } } ] } ]

{ "text": "Raw read data were processed using the Space Ranger pipeline. Downstream analyses were carried out in R using the Seurat pipeline.\nSource paper: PMC12133578" }

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 0, "end": 3, "text": "Raw", "labels": [ "Cell" ] } } ] } ]

{ "text": "Raw sequencing read data were processed with the Cell Ranger VDJ pipeline. Downstream analyses were carried out in R.\nSource paper: PMC12133578" }

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 0, "end": 3, "text": "Raw", "labels": [ "Cell" ] } } ] } ]

{ "text": "Additional details for computational data analysis are provided in Supplementary Methods .\nSource paper: PMC12133578" }

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{ "text": "Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article.\nSource paper: PMC12133578" }

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{ "text": "Online content\nSource paper: PMC12133578" }

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{ "text": "Any methods, additional references, Nature Portfolio reporting summaries, source data, extended data, supplementary information, acknowledgements, peer review information; details of author contributions and competing interests; and statements of data and code availability are available at 10.1038/s41590-0...

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{ "text": "PMC12256823\nSource paper: PMC12256823" }

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{ "text": "Bi-allelic variants in POPDC2 cause an autosomal recessive syndrome presenting with cardiac conduction defects and hypertrophic cardiomyopathy\nSource paper: PMC12256823" }

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{ "text": "Abstract\nSource paper: PMC12256823" }

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{ "text": "POPDC2 encodes the Popeye domain-containing protein 2, which has an important role in cardiac pacemaking and conduction, due in part to its cyclic AMP (cAMP)-dependent binding and regulation of TREK-1 potassium channels. Loss of Popdc2 in mice results in sinus pauses and bradycardia, and morpholino-mediate...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 1197, "end": 1203, "text": "hearts", "labels": [ "Tissue" ] } }, { "from_name": "label", ...

{ "text": "Introduction\nSource paper: PMC12256823" }

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{ "text": "The rhythmic contraction of the heart is orchestrated by the cardiac pacemaker and conduction system. Electrical activity in the heart arises in the sinus node, located in the right atrium near the entrance of the superior vena cava. The electrical impulse then spreads through the atria to the atrioventric...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 32, "end": 37, "text": "heart", "labels": [ "Tissue" ] } }, { "from_name": "label", ...

{ "text": "Cardiac conduction defects (CCDs; MIM: 115080 ) are primarily the consequence of age-related degeneration, structural heart disease, or post-operative complications. Presentation of CCDs in the young should raise suspicion of a genetic disorder. Rare variants in genes encoding cardiac ion channels (e.g., S...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 118, "end": 123, "text": "heart", "labels": [ "Tissue" ] } } ] } ]

{ "text": "Bi-allelic variants in POPDC1 (also known as BVES , MIM: 604577 ), encoding the Popeye domain-containing protein 1, are associated with muscular dystrophy and AV block (MIM: 604577 ). In mice, knockout of Popdc1 or Popdc2 resulted in stress-induced sinus pauses and sinus bradycardia. In zebrafish, morpholi...

[ { "result": [ { "from_name": "label", "to_name": "text", "type": "labels", "value": { "start": 878, "end": 882, "text": "node", "labels": [ "Tissue" ] } } ] } ]