Human gastrointestinal epithelia of the esophagus, stomach and duodenum resolved at single-cell resolution
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PROVIDER: PRJNA662498 | ENA |
REPOSITORIES: ENA
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Project description:The upper gastrointestinal tract consisting of the esophagus, stomach and duodenum controls food transport, digestion, nutrient uptake and hormone production. By single-cell analysis of healthy epithelia of these human organs, we molecularly defined their distinct cell types. We identified a quiescent COL17A1high stem/progenitor cell population within the basal cell layer of the esophagus and detected substantial gene expression differences between identical cell types of the human and mouse stomach. Selective and high expression of BEST4, CFTR, guanylin and uroguanylin identified the rare duodenal BCHE cells, which likely mediate high-volume fluid secretion due to continual activation of the CFTR channel by guanylin/uroguanylin-mediated autocrine signaling. Unexpectedly, the previously uncharacterized serotonin-producing enterochromaffin cells in the antral stomach significantly differ in gene expression from the duodenal enterochromaffin cells. We furthermore discovered that the histamine-producing enterochromaffin-like cells in the oxyntic stomach express luteinizing hormone, not previously seen in enteroendocrine cells.
2021-03-09 | GSE157694 | GEO
Project description:The upper gastrointestinal tract consisting of the esophagus, stomach and duodenum controls food transport, digestion, nutrient uptake and hormone production. By single-cell analysis of healthy epithelia of these human organs, we molecularly defined their distinct cell types. We identified a quiescent COL17A1high stem/progenitor cell population within the most basal cell layer of the esophagus and detected substantial gene expression differences between identical cell types of the human and mouse stomach. Selective and high expression of BEST4, CFTR, guanylin and uroguanylin identified a new rare cell type in the duodenum, referred to as BCHE cells, which likely mediate high-volume fluid secretion due to continual activation of the CFTR channel by guanylin/uroguanylin-mediated autocrine signaling. Previously uncharacterized serotonin-producing enterochromaffin cells in the antral stomach are shown to significantly differ in gene expression from the duodenal enterochromaffin cells. We furthermore discovered that the histamine-producing enterochromaffin-like cells in the oxyntic stomach express the luteinizing hormone, which was not previously seen in enteroendocrine cells.
| EGAS00001004695 | EGA
Project description:The gastroesophageal squamocolumnar junction (GE-SCJ) is a critical tissue interface between the esophagus and stomach, with significant relevance in the pathophysiology of gastrointestinal diseases. Despite this, the molecular mechanisms underlying GE-SCJ development remain unclear. Using single-cell transcriptomics, organoids, and spatial analysis, we examine the cellular heterogeneity and spatiotemporal dynamics of GE-SCJ development from embryonic to adult mice. We identify distinct transcriptional states and signaling pathways in the epithelial and mesenchymal compartments of the esophagus and stomach during development. Fibroblast-epithelial interactions are mediated by various signaling pathways, including WNT, BMP, TGF-β, FGF, EGF, and PDGF. Our results suggest that fibroblasts predominantly send FGF and TGF-β signals to the epithelia, while epithelial cells mainly send PDGF and EGF signals to fibroblasts. We observe differences in the ligands and receptors involved in cell-cell communication between the esophagus and stomach. Our findings provide insights into the molecular mechanisms underlying GE-SCJ development and fibroblast-epithelial crosstalk involved, paving the way to elucidate mechanisms during adaptive metaplasia development and carcinogenesis.
2024-03-12 | GSE181409 | GEO
Project description:In order to explore the functions of carbonic anhydrase VI (CAVI) more fully, we examined the transcriptomic responses to CAVI deficiency in the submandibular gland, stomach, and duodenum of Car6-/- mice by cDNA microarray. 94, 56, and 127 genes were up- or down-regulated in the above-mentioned tissues of Car6-/- mice, respectively. The functional clustering of differentially expressed genes revealed a number of altered biological processes. In the duodenum, the significantly affected biological pathways included immune system process and retinol metabolic process. Response to oxidative stress and brown fat cell differentiation changed remarkably in the submandibular gland. Notably, the submandibular gland, stomach, and duodenum shared one prominent transcriptional susceptibility pathway-catabolic process. Submandibular gland, stomach, and duodenum samples were collected from three wild-type and three Car6-/- female mice, respectively, at the age of two months. Total RNAs were purified and used for cDNA microarray.
2010-10-02 | E-GEOD-20423 | biostudies-arrayexpress
Project description:In order to explore the functions of carbonic anhydrase VI (CAVI) more fully, we examined the transcriptomic responses to CAVI deficiency in the submandibular gland, stomach, and duodenum of Car6-/- mice by cDNA microarray. 94, 56, and 127 genes were up- or down-regulated in the above-mentioned tissues of Car6-/- mice, respectively. The functional clustering of differentially expressed genes revealed a number of altered biological processes. In the duodenum, the significantly affected biological pathways included immune system process and retinol metabolic process. Response to oxidative stress and brown fat cell differentiation changed remarkably in the submandibular gland. Notably, the submandibular gland, stomach, and duodenum shared one prominent transcriptional susceptibility pathway-catabolic process.
2010-10-02 | GSE20423 | GEO
Project description:single cell sequencing esophagus, stomach and duodenum of :
4 esophagus samples
9 gastric samples
5 duodenum samples
| EGAD00001006417 | EGA
Project description:In the adult mouse, distinct morphological and transcriptional differences separate stomach from intestinal epithelium. Remarkably, the epithelial boundary between these two organs is literally one cell thick. This discrete junction is established suddenly and precisely at embryonic day (E) 16.5, by sharpening a previously diffuse intermediate zone. In the present study, we define the dynamic transcriptome of stomach, pylorus and intestinal tissues between E14.5 and E16.5. We show that establishment of this boundary is concomitant with the induction of over a thousand genes in intestinal epithelium, and these gene products provide intestinal character. Hence, we call this process intestinalization. We identify specific transcription factors (Hnf4g, Creb3l3 and Tcfec) and examine signaling pathways (Hedgehog and Wnt) that may play a role in this process. Finally, we define a unique expression domain at the pylorus itself and detect novel pylorus-specific patterns for the transcription factor Gata3 and the secreted protein nephrocan. Experiment Overall Design: Stomach, pylorus and duodenum tissue from E14.5 and E16.5 mouse embryos were collected for RNA extraction and hybridization on Affymetrix microarrays. We sought to study the gene expression profiles and identify genes and pathways enriched in these three tissues at two important developmental times.
2009-10-09 | E-GEOD-15872 | biostudies-arrayexpress
Project description:Background & Aims: Tissue metaplasia is uncommon in adults because established cis-element programs resist rewiring. In Barrett’s esophagus, the distal esophageal mucosa acquires predominantly intestinal character, with notable gastric features, and is predisposed to develop invasive cancers. We sought to understand the chromatin underpinnings of Barrett’s metaplasia and why it commonly displays simultaneous gastric and intestinal properties. Methods: We profiled cis-regulatory elements with active histone modifications in primary human biopsy materials using chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq). Mutations in Barrett’s esophagus were examined in relation to tissue-specific enhancer landscapes using a random-forest machine learning algorithm. We also profiled open chromatin at single-cell resolution in primary Barrett’s biopsy specimens using the assay for transposase-accessible chromatin (ATAC-seq). We used one- and two-color immunohistochemistry to examine protein expression of tissue-restricted genes. Results: Barrett’s esophagus bears epigenome fingerprints of human stomach and intestinal columnar, but not esophageal squamous, epithelia. Mutational patterns were best explained as arising on the epigenome background of active gastric cis-elements, supporting the view that adjoining stomach epithelium is a likely tissue source. Individual cells in Barrett’s metaplasia co-express gastric and intestinal genes, reflecting concomitant chromatin access at enhancers ordinarily restricted to one or the other epithelium. Protein expression of stomach-specific mucins, CLDN18, and a novel gastric marker, ANXA10, revealed extensive tissue and sub-clonal heterogeneity of dual stomach-intestinal cell states. Conclusions: These findings reveal mixed and dynamic tissue-restricted chromatin states and phenotypic heterogeneity in Barrett’s esophagus. Pervasive intra-gland variation argues against stem-cell governance of this phenotype.
2021-06-03 | GSE97178 | GEO
Project description:samples contain normal, Berret and duodenum and adenocarcinoma
2006-11-13 | E-SMDB-3834 | biostudies-arrayexpress
Project description:samples contain normal, Barrett and duodenum and adenocarcinoma BACKGROUND & AIMS: Barrett's esophagus is a precursor of esophageal adenocarcinoma. DNA microarrays that enable a genome-wide assessment of gene expression enhance the identification of specific genes as well as gene expression patterns that are expressed by Barrett's esophagus and adenocarcinoma compared with normal tissues. Barrett's esophagus length has also been identified as a risk factor for progression to adenocarcinoma, but whether there are intrinsic biological differences between short-segment and long-segment Barrett's esophagus can be explored with microarrays. METHODS: Gene expression profiles for endoscopically obtained biopsy specimens of Barrett's esophagus or esophageal adenocarcinoma and associated normal esophagus and duodenum were identified for 17 patients using DNA microarrays. Unsupervised and supervised approaches for data analysis defined similarities and differences between the tissues as well as correlations with clinical phenotypes. RESULTS: Each tissue displays a unique expression profile that distinguishes it from others. Barrett's esophagus and esophageal adenocarcinoma express a unique set of stromal genes that is distinct from normal tissues but similar to other cancers. Adenocarcinoma also showed lower and higher expression for many genes compared with Barrett's esophagus. No difference in gene expression was found between short-segment and long-segment Barrett's esophagus. CONCLUSIONS: The genome-wide assessment provided by current DNA microarrays reveals many candidate genes and patterns not previously identified. Stromal gene expression in Barrett's esophagus and adenocarcinoma is similar, indicating that these changes precede malignant transformation. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Keywords: disease_state_design
2006-10-18 | GSE6059 | GEO