PMCID
stringclasses 24
values | Title
stringclasses 24
values | Sentences
stringlengths 2
40.7k
|
|---|---|---|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Fig. 2ECs in CD.a, UMAP plot of small intestinal epithelial EPCAM cells in HCs (n = 3) and in participants with CD (n = 5).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
b, Bubble plot showing the expression of selected genes defining specific cluster identities.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Scaled gene expression indicated by color; proportion of cells expressing the gene indicated by bubble size.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
c, Local neighborhood enrichment of EPCAM cells in ACD versus HCs.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Color indicates enrichment (log fold change (FC)) of cells in ACD versus HCs in that UMAP neighborhood; size of dot indicates false discovery rate (FDR)-adjusted −log10 values.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
d, TA cells (left) and early enterocytes (right) in HCs and CD, as a proportion of total EPCAM cells.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
e, Pseudotime trajectory of gene expression of EPCAM ECs, colored by pseudotime axis (left), cluster identity (middle) and lineage (right).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Arrows indicate putative direction of cell differentiation.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
f, Density of cells along pseudotime trajectory axis split by disease state: ACD (red), TCD (blue) and HCs (gray).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
g, Smoothed heat map showing expression of selected genes related to intestinal absorption along pseudotime trajectories relating to secretory (toward left) and absorptive (toward right) lineage.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
h, Volcano plot displaying differentially expressed gene transcripts between HCs and ACD in total ECs.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
d, Unpaired two-tailed t-test.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Data are presented as mean values ± s.e.m.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
a, UMAP plot of small intestinal epithelial EPCAM cells in HCs (n = 3) and in participants with CD (n = 5).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
b, Bubble plot showing the expression of selected genes defining specific cluster identities.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Scaled gene expression indicated by color; proportion of cells expressing the gene indicated by bubble size.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
c, Local neighborhood enrichment of EPCAM cells in ACD versus HCs.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Color indicates enrichment (log fold change (FC)) of cells in ACD versus HCs in that UMAP neighborhood; size of dot indicates false discovery rate (FDR)-adjusted −log10 values.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
d, TA cells (left) and early enterocytes (right) in HCs and CD, as a proportion of total EPCAM cells.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
e, Pseudotime trajectory of gene expression of EPCAM ECs, colored by pseudotime axis (left), cluster identity (middle) and lineage (right).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Arrows indicate putative direction of cell differentiation.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
f, Density of cells along pseudotime trajectory axis split by disease state: ACD (red), TCD (blue) and HCs (gray).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
g, Smoothed heat map showing expression of selected genes related to intestinal absorption along pseudotime trajectories relating to secretory (toward left) and absorptive (toward right) lineage.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
h, Volcano plot displaying differentially expressed gene transcripts between HCs and ACD in total ECs.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
d, Unpaired two-tailed t-test.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Data are presented as mean values ± s.e.m.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
A LYZ Paneth cell-like population (MMP7REG1ASOD3PLA2G2A) was also identified (Fig. 2a,b), although defensin gene expression was not detected.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
This population expressed PGC, mucins including MUC5AC, MUC1 and MUC6 and AQP5, suggesting it also contained Brunner’s gland cells or ectopic gastric pyloric gland cells.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
This cell type was enriched in active celiac disease (ACD; Fig. 2c,d), perhaps in response to IFNγ.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Thus, this population could represent inflammation-driven gastric cell metaplasia.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
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).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
This persisted in treated celiac disease (TCD; Extended Data Fig. 1b,c).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
In parallel, more actively cycling ECs were observed in ACD and TCD (Extended Data Fig. 1d,e).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Pseudotime analyses identified epithelial developmental trajectories, from undifferentiated progenitor states toward absorptive and secretory lineages (Fig. 2e).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
In CD, ECs were shifted to earlier pseudotime states, with loss of mature ECs (Fig. 2f).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
CCL25, encoding the ligand for CCR9 (implicated in CD pathogenesis), was expressed predominantly by progenitor cells (Fig. 2b and Extended Data Fig. 1f).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
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 enteroendocrine cells (EECs; peptide hormone processing/secretion).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Mature enterocytes expressed key metabolic and macronutrient catabolic pathways, and active transport and absorption mechanisms.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Early ECs and TA cells did not express these pathways.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Absorptive function genes were limited to cell states at the end of absorptive epithelium pseudotime trajectories, consistent with EC development along the crypt–villus axis (Fig. 2g).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Notably, gene sets related to lipid, carbohydrate, cholesterol, vitamin and iron processing and absorption were all downregulated in mature enterocytes in ACD (Extended Data Fig. 1g–i).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
These transcriptional changes normalized in TCD, although some pathways, including fructose metabolism and lipid catabolism, remained reduced (Extended Data Fig. 1h).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Overall, absorptive capacity is reduced in ACD not simply by reduction in villus surface area, but through a relative increase of EC progenitors lacking absorptive machinery, and pathway downregulation in mature enterocytes.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
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).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Interferon-stimulated genes (types I and II) dominated the epithelial response, including STAT1 (Fig. 2h and Supplementary Table 5).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
The major disease-associated responses were observed in all EC lineages (Extended Data Fig. 1j–l), including antigen-presentation pathways, type I/II interferon responses, lymphocyte-mediated immunity and cytotoxicity and cell adhesion regulation (Extended Data Fig. 1m,n).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Some transcriptional changes were cell-type specific.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
IL32 was highly expressed in ACD by mature enterocytes (Extended Data Fig. 1k), perhaps regulated by interferons.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
The reduction of fatty acid catabolism/transport (APOA1, FABP2), metal ion transport (iron: FTH1, FTL; zinc: SLC39A4) and carbohydrate metabolism (ALDOB, PCK1) was restricted to absorptive lineages, mainly mature enterocytes (Extended Data Fig. 1k,n).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Progenitor cells upregulated genes associated with cell division and differentiation, and downregulated those associated with tissue repair and homeostasis (Extended Data Fig. 1m,n).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Secretory lineages showed increased expression of gut hormone genes, LYZ, and chemokines (CXCL17, CXCL2; Extended Data Fig. 1l).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
The duodenum, where CD inflammation predominates, has sensory and neurohormonal functions.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
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).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
EEC proportions altered in CD, with increases in NEUROG3 progenitor cells and somatostatin-producing D cells (Extended Data Fig. 2i–k).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
In adults (dataset 1), CD4 T cells formed subsets dominated by TH1-polarized and IL-17-producing helper T (TH17)-polarized effectors, as well as small naive and FOXP3 regulatory populations (Fig. 3a–c and Supplementary Table 6).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
There was a cluster of TFH-like CD4 T cells expressing PDCD1, BTLA, CD28, ICOS and intermediate CXCR5.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Dataset 2 (pediatric) contained analogous subsets (Extended Data Fig. 3a), including CD31CR2 recent thymic emigrants, a CCR7 TFH-like subset and the TFH-like subset expressing PD1, ICOS, CTLA4, BTLA and CD161 at the protein level (Fig. 3d,e).Fig.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
3CD4 T cells in CD.a–c, Intestinal CD4 T cells in health and CD in dataset 1 (adult—10x Genomics).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
a, UMAP plot of intestinal CD4 T cells in health and CD (n = 8).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
b, Bubble plot showing the expression of selected genes defining specific cluster identities.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Scaled gene expression indicated by color; proportion of cells expressing the gene indicated by bubble size.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
c, CD4 T cell UMAP plots overlaid with expression of TNFSF8, PDCD1, TOX2, CXCR3, CXCL13, CD200, CXCR5 and TRBV7-2.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Intestinal CD4 T cells in health and CD in dataset 2 (pediatric—BD Rhapsody; d–f).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
d, UMAP plot of intestinal CD4 T cells in health and CD (n = 15).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
e, Bubble plot showing the expression of selected genes and proteins defining specific cluster identities.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Scaled gene/protein expression indicated by color; proportion of cells expressing the gene/protein indicated by bubble size.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
f, Local neighborhood enrichment of CD4 cells in ACD versus HCs (dataset 1).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Color indicates enrichment (log fold change) of cells in ACD versus HCs in that UMAP neighborhood; size of dot indicates −log10FDR.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
g, Scatterplot of mean proportion (± s.e.)
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
of CD4 T cell clusters in HCs (n = 3) versus ACD (n = 5) in dataset 1.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Clusters above the line of unity are enriched in ACD.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
h,i, Treg (h) and TFH (i) CD4 T cell populations in HCs and CD, as a proportion of total CD4 T cells in dataset 1 (HCs n = 3, ACD n = 5) and dataset 2 (HCs n = 5, ACD n = 10).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
j, UMAP plot of CD4 T cells in dataset 2, overlaid with IL21 and IFNG expression.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
k, UMAP plot of CD4 T cells in dataset 1, overlaid with CXCL13, IL21, IFNG and TNFSF8 expression.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
h,i, Two-sided Mann–Whitney test.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Data are presented as mean values ± s.e.m.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Ab, antibody; Tc17, IL17CD8 T cells; DP, CD4CD8 double positive cells.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
a–c, Intestinal CD4 T cells in health and CD in dataset 1 (adult—10x Genomics).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
a, UMAP plot of intestinal CD4 T cells in health and CD (n = 8).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
b, Bubble plot showing the expression of selected genes defining specific cluster identities.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Scaled gene expression indicated by color; proportion of cells expressing the gene indicated by bubble size.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
c, CD4 T cell UMAP plots overlaid with expression of TNFSF8, PDCD1, TOX2, CXCR3, CXCL13, CD200, CXCR5 and TRBV7-2.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Intestinal CD4 T cells in health and CD in dataset 2 (pediatric—BD Rhapsody; d–f).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
d, UMAP plot of intestinal CD4 T cells in health and CD (n = 15).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
e, Bubble plot showing the expression of selected genes and proteins defining specific cluster identities.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Scaled gene/protein expression indicated by color; proportion of cells expressing the gene/protein indicated by bubble size.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
f, Local neighborhood enrichment of CD4 cells in ACD versus HCs (dataset 1).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Color indicates enrichment (log fold change) of cells in ACD versus HCs in that UMAP neighborhood; size of dot indicates −log10FDR.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
g, Scatterplot of mean proportion (± s.e.)
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
of CD4 T cell clusters in HCs (n = 3) versus ACD (n = 5) in dataset 1.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Clusters above the line of unity are enriched in ACD.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
h,i, Treg (h) and TFH (i) CD4 T cell populations in HCs and CD, as a proportion of total CD4 T cells in dataset 1 (HCs n = 3, ACD n = 5) and dataset 2 (HCs n = 5, ACD n = 10).
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
j, UMAP plot of CD4 T cells in dataset 2, overlaid with IL21 and IFNG expression.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
k, UMAP plot of CD4 T cells in dataset 1, overlaid with CXCL13, IL21, IFNG and TNFSF8 expression.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
h,i, Two-sided Mann–Whitney test.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Data are presented as mean values ± s.e.m.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Ab, antibody; Tc17, IL17CD8 T cells; DP, CD4CD8 double positive cells.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
This TFH-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.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
The cluster showed enrichment of TRBV7-2, a V-gene enriched in gluten-specific CD4 T cell HLA-DQ2.5 TCR repertoires.
|
PMC12133578
|
Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease.
|
Treg and TFH-like CD4 T cells were increased in ACD in adults and children (Fig. 3f–i).
|
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.