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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 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.

PROVIDER: EGAS00001004695 | EGA |

REPOSITORIES: EGA

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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 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

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

CFTR is a tumor suppressor gene in murine and human intestinal cancer [microarray]

Project description:Analysis of the cystic fibrosis gene Cftr in the colon and small intestine of Cftr-deficient murine model. The hypothesis was loss of Cftr altered expression of genes important in intestinal homeostasis and oncogenic signaling pathways. The results identified potential roles of Cftr in up- or down-regulating major gene clusters that belong to groups of immune response, ion channel, intestinal stem cell and other growth regulators. Total RNA was isolated from the normal intestine of three Apc wildtype Cftr wildtype and three Apc Cftr-deficient mice. For the colon intestinal epithelia from the same region of the distal colon of each mouse was separated from the rest of the intestine prior to RNA isolation. Therefore RNA was obtained from only epithelial cells. For the small intestine, a section of the mid-duodenum from each mouse was sheared of villi prior to RNA isolation. Therefore RNA was obtained from whole duodenum (minus villi), containing epithelia cells but also stromal and other cells. RNA Seq was then conducted on all samples, with at least two replicates for each biological sample.

2015-12-15 | E-GEOD-75996 | biostudies-arrayexpress

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

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

| PRJNA662498 | ENA

Gene expression profiling of gastroesophageal adenocarcinoma

Project description:We aimed to genetically characterize adenocarcinomas in the gastroesophagel junction in relation to cancers in the esophagus and the stomach. In total 27 tumors was genetically profiled using gene expression array. Adenocarcinomas located in the gastroesophageal junction showed strong similarites with tumors in the distal esophagus, whereas different profiles were generated for tumors in the proximal stomach. Three types of gastroesophageal adenocarcinomas; 10 distal esophageal (EA) tumors, 9 junctional (JA) and 8 proximal stomach cancers (GA) was undergone differentially analysis based on gene expression profiles. One replicate of tumor ID 27_JA (replicate ID 27_JA_2) and one replicate of tumor ID 3-GA (replicate ID 3-GA-2). Reference samples consist of the Stratagene Universal Reference (10 cellines), commercially obtained from Stratagene, La Jolla, CA, USA.

2010-05-29 | E-GEOD-22050 | biostudies-arrayexpress

Peptidomics profiling of human intestine

Project description:The aim of the project is to generate a peptidomics map of gut hormone peptides along the gastrointestinal tract, starting with the stomach and including the duodenum, jejunum, ileum, ascending colon, sigmoid colon and rectum. The tissues would be collected after surgery and the peptide fraction extracted and anlysed by nano LC-MS to identify what peptide hormones are present. These data will then be used to compare against the human transcriptome, and also for comparison against equivent peptides from murine intestinal extracts.

2019-02-15 | PXD009788 | Pride

Peptidomics profiling of murine intestine

Project description:The aim of the project is to generate a peptidomics map of gut hormone peptides along the gastrointestinal tract, starting with the stomach and including the duodenum, jejunum, ileum, colon and rectum. The tissues would be collected after surgery and the peptide fraction extracted and anlysed by nano LC-MS to identify what peptide hormones are present. These data will then be used to compare against the murine transcriptome, and also for comparison against equivent peptides from human intestinal extracts.

2019-02-15 | PXD009796 | Pride

Secretory Cells Dominate Airway CFTR Expression and Function in Human Airway Superficial Epithelia [bulk RNA]

Project description:Purpose: To identify the cell types that contribute to CFTR expression and function within the proximal-distal axis of the normal human lung. Methods: Single cell RNA-seq (scRNA-seq) was performed on freshly isolated human large and small airway epithelial cells. Single cell-based RNA in situ hybridization (scRNA-ISH) and quantitative RT-PCR (scqRT-PCR) were performed for validation. In vitro culture systems correlated CFTR function to cell types. Lentiviruses were used for cell-type specific transduction of wild-type CFTR in CF cells. Results: scRNA-seq identified secretory cells as dominating CFTR expression in normal human large and particularly small airways, followed by basal cells. Ionocytes expressed the highest CFTR levels but were rare, while expression in ciliated cells was infrequent and low. scRNA-ISH, and scqRT-PCR confirmed the scRNA-seq findings. CF lungs exhibited distributions of CFTR and ionocytes similar to normal controls. CFTR-mediated Cl- secretion tracked secretory cell, not ionocyte, densities. Further, the nucleotide-purinergic regulatory system that controls CFTR-mediated hydration was associated with secretory cells. Lentiviral transduction of wild-type CFTR produced CFTR-mediated Cl- secretion in CF airway secretory cells but not ciliated cells. Conclusions: Secretory cells dominate CFTR expression and function in human airway superficial epithelia. CFTR therapies may need to restore CFTR function to multiple cell types, with a focus on secretory cells.

2020-12-16 | GSE160674 | GEO

Secretory Cells Dominate Airway CFTR Expression and Function in Human Airway Superficial Epithelia [single-cell RNA-seq]

2020-12-16 | GSE160673 | GEO

Gene expression profiling in the submandibular gland, stomach, and duodenum of CAVI-deficient mice

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

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