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Human gastrointestinal epithelia of the esophagus, stomach and duodenum resolved at single-cell resolution

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE157694 | GEO | 2021/03/09

REPOSITORIES: GEO

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Human gastrointestinal epithelia of the esophagus, stomach and duodenum resolved at single-cell resolution

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

Unbiased transcription factor CRISPR screen identifies ZNF800 as master repressor of enteroendocrine differentiation [screen]

Project description:Enteroendocrine cells (EECs) are hormone-producing cells residing in the epithelium of stomach, small intestine (SI) and colon. EECs regulate various aspects of metabolic activity including insulin levels, satiety, gastrointestinal secretion and motility. The generation of different EEC lineages of the SI is incompletely understood. We now report a TFome-wide CRISPR knockout screen in adult human intestinal organoids to identify dominant transcription factors controlling EEC differentiation. ZNF800 is discovered as a master repressor for endocrine lineage commitment, which particularly restricts enterochromaffin cell differentiation by directly controlling an endocrine TF network centered on PAX4. Thus, organoid models allow unbiased functional SCRISPR screens for genes that program cell differentiation.

2023-10-27 | GSE229584 | GEO

Unbiased transcription factor CRISPR screen identifies ZNF800 as master repressor of enteroendocrine differentiation [scRNA-seq]

2023-10-27 | GSE229585 | GEO

Unbiased transcription factor CRISPR screen identifies ZNF800 as master repressor of enteroendocrine differentiation [CHIP-seq]

2023-10-27 | GSE229583 | GEO

Distinct Cellular Origins for Serotonin-Expressing and Enterochromaffin-like Cells in the Gastric Corpus

Project description:The alimentary tract contains a diffuse endocrine system comprising enteroendocrine cells that secrete peptides or biogenic amines to regulate digestion, insulin secretion, food intake, and energy homeostasis. Lineage analysis in the stomach revealed that a significant fraction of endocrine cells in the gastric corpus did not arise from neurogenin3-expressing cells, unlike enteroendocrine cells elsewhere in the digestive tract. We aimed to isolate enriched serotonin-secreting and enterochromaffin-like (ECL) cells from the stomach and to clarify their cellular origin. We used Neurod1 and Neurog3 lineage analysis, and examined differentiation of serotonin-producing and ECL cells in stomach tissues of Neurod1-cre;ROSAtdTom, Tph1-CFP, c-Kitwsh/wsh, and Neurog3Cre;ROSAtdTom mice, by immunohistochemistry. We used fluorescence-activated cell sorting to isolate each cell type for gene expression analysis. We performed RNA-seq analysis of ECL cells. Neither serotonin-secreting nor ECL cells of the corpus arose from cells expressing Neurod1. Serotonin-secreting cells expressed a number of mast cell genes, but not genes associated with endocrine differentiation; they did not develop in c-Kitwsh/wsh mice and were labeled with transplanted bone marrow cells. RNA-seq analysis of ECL cells revealed high expression levels of many genes common to endocrine cells including transcription factors, hormones, ion channels, and solute transporters but not markers of bone marrow cells. We used fluorescence-activated cell sorting to isolate Hdc+ cells from stomach corpus and performed RNA-seq for gene expression analysis to determine the origin of those cells.

2013-12-12 | E-GEOD-53214 | biostudies-arrayexpress

Effects of a gastrin receptor antagonist (NTZ, previously named YF) on the gastric corpus mucosa of HKATPase betasubunit knockout (KO) mice

Project description:Purpose: the effects of a gastrin receptor antagonist has been studies in patients with gastrin neuroendocrine (NE) tumours due to hypergastrinemia. This mouse model of hypergastrinemia is a model for studying long term acid inhibition, including NE hyperplasia and formation of Spasmolytic polypeptide expressing metaplasia (SPEM), a proposed premalignant alteration of the stomach. Methods: RNA was isolated from the oxyntic mucosa. RNA was sequenced using standard Illumina protocols on a NextSeq 500 instrument. Results: NTZ reduced oxyntic mucosal hypertropohy and stomach weight. Neuroendocrine cell hyperplasia and NE markers were also reduced. Spasmolytic polypeptide expressing metaplasia (SPEM) was expressed in KO mice and was not affected by the gastrin receptor antagonist. Conclusions: The gastrin receptor antagonist YF reduced gastric corpus mucosal hypertrophy and NE cell hyperplasia in HKATPase KO mice, but did not affect SPEM or SPEM related genes.

2019-12-23 | GSE142513 | GEO

e4e94fff-a46f-4a63-a2e8-96ace38b89c4 - samples

Project description:single cell sequencing esophagus, stomach and duodenum of : 4 esophagus samples 9 gastric samples 5 duodenum samples

| EGAD00001006417 | EGA

Transcriptional profiles of stomach organoids from human embryonic stem cells.

Project description:Gastric ulcer, which affect many of patients and is deeply related with gastric cancer, is caused by chronic gastric acid stimulation. Stomach fundus, the main body of stomach, is a major source of gastric acid and peptidase for food digestion. Recapturing the main body of stomach requires mainly 3 functionally differentiated cells; parietal (oxyntic) cells, chief (zymogenic) cells, and surface mucous foveolar (pit) cells. We have previously shown the induction of stomach tissue with functional secreting activities by directed differentiation of mouse embryonic stem cells (ES cells) to stomach primordium with both gut epithelium and splanchnic mesoderm. However, generating human stomach with fundus and such functions has been elucidated and a long-desired goal. Here, we describe the method for establishing human embryonic stem cell-derived stomach organoids with fundus gland structure. Along with mouse stomach development and de novo stomach generation from mouse ES cells in vitro, we observed gut-like structure formation from human embryonic stem cells by induction of both endoderm and mesoderm. These human embryonic gut could differentiate into stomach primordium by growth factor stimulation as well as stomach development, and form stomach tissue in three-dimensional organoid culture. Furthermore, these stomach organoids contain fundus-like gland with parietal cells and chief cells, some of secreting activities, and is transcriptionally close to human stomach. Human functional stomach derived from embryonic stem cells represent powerful tools for analying human stomach development, and gastric ulcer related disease including gastric tumorgenesis.

2017-08-31 | GSE79673 | GEO

Distinct Cellular Origins for Serotonin-Expressing and Enterochromaffin-like Cells in the Gastric Corpus

2013-12-12 | GSE53214 | GEO

Expression profiling across mouse epithelial tissues

Project description:To characterize genes, pathways, and transcriptional regulators enriched in the mouse cornea, we compared the expression profiles of whole mouse cornea, bladder, esophagus, lung, proximal small intestine, skin, stomach, and trachea. Total RNA was purified from esophagus, lung, proximal small intestine, skin, stomach, and trachea. Data from previous studies in the lab (cornea, GSE43155; bladder, GSE15770; and E18.5 skin, GSE15772) were utilized in the comparison.

2013-01-15 | E-GEOD-43381 | biostudies-arrayexpress

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