Enhancing single-cell cellular state inference by incorporating molecular network features
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE140288 | GEO | 2021/05/12
REPOSITORIES: GEO
Similar Datasets
Project description:Background & Aims: We have recently established long-term culture conditions under which single crypts or stem cells derived from murine small intestine expand over long periods of time. Growing crypts undergo multiple crypt fission events, whilst simultaneously generating villus-like epithelial domains in which all differentiated cell types are present. We have now adapted the culture conditions to grow similar epithelial organoids from mouse colon and human small intestine and colon. Methods: Based on the murine small intestinal culture system, we optimized the murine and human colon culture system. Results: Addition of Wnt3A to the growth factor cocktail allowed mouse colon crypts to expand indefinitely. Further addition of nicotinamide, a small molecule Alk inhibitor and a p38 inhibitor was essential for long-term human small intestine and colon culture. The culture system also allowed growth of murine Apcmin adenomas, human colorectal cancer and human esophageal metaplastic Barrett’s epithelium. Conclusion: The culture technology should be widely applicable as a research tool for infectious, inflammatory and neoplastic pathologies of the human gastrointestinal tract. Moreover, regenerative applications may become feasible with ex vivo expanded intestinal epithelia.
2011-12-07 | GSE28907 | GEO
Project description:Gene expression was compared between adult wildtype (WT) CD1 jejunual epithelium (J) and ileal epithleium (I). Gene expression was compared between adult control ileal epithleium and Gata4 conditional knockin (cKI) ileal epithelium. Gene expression was compared between adult wildtype CD1 jejunum and Gata4 conditional knockout (cKO) jejunal epithelium.
2017-03-01 | GSE75870 | GEO
Project description:Background & Aims: We have recently established long-term culture conditions under which single crypts or stem cells derived from murine small intestine expand over long periods of time. Growing crypts undergo multiple crypt fission events, whilst simultaneously generating villus-like epithelial domains in which all differentiated cell types are present. We have now adapted the culture conditions to grow similar epithelial organoids from mouse colon and human small intestine and colon. Methods: Based on the murine small intestinal culture system, we optimized the murine and human colon culture system. Results: Addition of Wnt3A to the growth factor cocktail allowed mouse colon crypts to expand indefinitely. Further addition of nicotinamide, a small molecule Alk inhibitor and a p38 inhibitor was essential for long-term human small intestine and colon culture. The culture system also allowed growth of murine Apcmin adenomas, human colorectal cancer and human esophageal metaplastic Barrett’s epithelium. Conclusion: The culture technology should be widely applicable as a research tool for infectious, inflammatory and neoplastic pathologies of the human gastrointestinal tract. Moreover, regenerative applications may become feasible with ex vivo expanded intestinal epithelia. Human organoids were grown embedded in Matrigel in HISC (Human intestinal stem cell culture) medium. Additionally, human small intestinal crypts and villi were isolated independently from a freshly operated sample. RNA was isolated using the RNeasy Micro kit (Qiagen). Samples were labled according to Agilent guidelines with Cy3, whereas human reference RNA (Stratagene) was labeled in Cy5. Feature Extraction Software was used to extract and normalize data.
2011-12-07 | E-GEOD-28907 | biostudies-arrayexpress
Project description:GATA4 is expressed in the proximal 85% of small intestine where it promotes a proximal intestinal ('jejunal') identity while repressing a distal intestinal ('ileal') identity, but its molecular mechanisms are unclear. Here, we tested the hypothesis that GATA4 promotes a jejunal versus ileal identity in mouse intestine by directly activating and repressing specific subsets of absorptive enterocyte genes by modulating the acetylation of histone H3, lysine 27 (H3K27), a mark of active chromatin, at sites of GATA4 occupancy. Global analysis of mouse jejunal epithelium showed a statistically significant association of GATA4 occupancy with GATA4-regulated genes. Occupancy was equally distributed between down- and up-regulated targets, and occupancy sites showed a dichotomy of unique motif over-representation at down- versus up-regulated genes. H3K27ac enrichment at GATA4-binding loci that mapped to down-regulated genes (activation targets) was elevated, changed little upon conditional Gata4 deletion, and was similar to control ileum, whereas H3K27ac enrichment at GATA4-binding loci that mapped to up-regulated genes (repression targets) was depleted, increased upon conditional Gata4 deletion, and approached H3K27ac enrichment in wild-type control ileum. These data support the hypothesis that GATA4 both activates and represses intestinal genes, and show that GATA4 represses an ileal program of gene expression in the proximal small intestine by inhibiting the acetylation of H3K27. 2 samples were analyzed (1 ChIPseq, 1 input sample), control was done by confirming ChIP-qPCR on specific targets
2015-05-16 | E-GEOD-68957 | biostudies-arrayexpress
Project description:To establish better understanding of cells found in jejunal and ileal Peyer's patches of pigs, we utilized single-cell RNA sequencing scRNA-seq and spatial transcriptomics to recover and analyze cells and spatial regions from sections of jejunum and ileum containing Peyer's patches. Cells identified via single-cell RNA sequencing included B, T/innate lymphoid cell, myeloid, epithelial, and stromal lineage cells. Spatial dots recovered via spatial transcriptomics belonged to regions including villi, crypts, interfollicular/parafollicular zones, follicles, and muscularis. Overall, results provide new information on regional localization and transcriptional profiles of cells in the pig small intestine.
2023-09-12 | GSE232605 | GEO
Project description:The small intestine is responsible for nutrient absorption and it is one of the most important interfaces between the environment and our body. During aging, changes in the structure of the epithelium lead to food malabsorption and reduced barrier function thus increasing disease risk in aging. The molecular drivers of these alterations remain poorly understood. Here, we compared the proteomes of small intestinal crypts from mice across different anatomical regions and age groups. We found that aging alters epithelial immune responses, metabolic networks and stem cell proliferation, and it is accompanied by a region-dependent skewing in the cellular composition of the intestinal epithelium. Of note, a short period of dietary restriction followed by re-feeding partially restores the epithelium to a youthful state by promoting the differentiation of intestinal stem cells (ISCs) towards the secretory lineage. Using in vitro and in vivo studies, we identify Hmgcs2 (3-hydroxy-3-methylglutaryl-CoA synthetase 2) – the rate limiting enzyme in the synthesis of ketone bodies – as a modulator of ISCs differentiation, which responds to dietary changes. This study provides an atlas of age-dependent proteome changes in defined regions of the intestinal epithelium and characterizes how young and old mice adapt to drastic changes of diet, such as dietary restriction and re-feeding.
2020-04-29 | PXD014311 | Pride
Project description:We used microarray to analyze the global gene expression in crypts isolated from wild-type (Lpcat3F/F) and Lpcat3 tamoxifen inducible intestine-specific knockout (Lpcat3F/F, Villin-CreERT2) crypts. Phospholipid remodeling is a critical determinant of membrane composition and function. How membrane phospholipid composition affects tissue stem cell function and tumorigenesis is unknown. Here we demonstrate that Lpcat3-dependent phospholipid remodeling regulates intestinal stem cell (ISC) proliferation and promotes tumorigenesis in intestine. The objective of generating this dataset was to analyze the effects of Lpcat3 loss of function on gene expression in mouse intestine crypts.
2017-12-05 | GSE98516 | GEO
Project description:In vitro 2D cultures of intestinal epithelial cells or epithelial cell lines have been widely used to study cell function and host-pathogen interactions in the bovine intestine. However, these cultures lack the cellular diversity encountered in the intestinal epithelium, and the physiological relevance of monocultures of transformed cell lines is uncertain. Little is also known of the factors that influence cell differentiation and homeostasis in the bovine intestinal epithelium, and few cell-specific markers that can distinguish the different intestinal epithelial cell lineages have been reported. Here we describe a simple and reliable procedure to establish in vitro 3D enteroid, or “mini gut”, cultures from bovine small intestinal (ileal) crypts. These enteroids contained a continuous central lumen lined with a single layer of polarized enterocytes, bound by tight junctions with abundant microvilli on their apical surfaces. Histological and transcriptional analyses suggested that the enteroids comprised a mixed population of intestinal epithelial cell lineages including intestinal stem cells, enterocytes, Paneth cells, goblet cells and enteroendocrine cells. We show that bovine enteroids can be successfully maintained long-term through multiple serial passages without observable changes to their growth characteristics, morphology or transcriptome. Furthermore, the bovine enteroids can be cryopreserved and viable cultures recovered from frozen stocks. Our data suggest that these 3D bovine enteroid cultures represent a novel, physiologically-relevant and tractable in vitro system in which epithelial cell differentiation and function, and host-pathogen interactions in the bovine small intestine can be studied.
2018-07-10 | GSE112674 | GEO
Project description:Our genome-wide gene expression data indicate that, despite the lack of crypts, the rostral, mid, and caudal portions of the zebrafish intestine have distinct functions analogous to the mammalian small and large intestine, respectively. Organization of ridge structures represents a unique feature of zebrafish intestine, though they produce similar cross sections to mammalian intestines. Evolutionary lack of stomach, crypts, Paneth cells and submucosal glands has shaped the zebrafish intestine into a simpler but unique organ in vertebrate intestinal biology.
2010-06-29 | GSE20884 | GEO
Project description:This dataset includes RNA-seq data from ileal and colonic biopsies at time of diagnosis for treatment-naive, uncomplicated Crohn's disease (CD) patients and matched controls. This is includes 56 CD patients each for ileal and colonic tissue and for controls, 46 colonic samples and 45 ileal samples. Clinical characteristics such as development of complications, disease remission, or progression to surgery were recorded with a mean follow-up of 6 years.
2024-02-07 | GSE221161 | GEO