Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA330979 | ENA |
REPOSITORIES: ENA
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Project description:Analysis of the complex expression of claudin genes and transcription factors during intestinal epithelial cell differentiation across the crypt-to-surface colonic axis. Characterization of the complex expression gradients of transcription factors Hopx, Hnf4a, Klf4 and Tcfl2 and 12 claudin genes. In vitro confirmatory methods identified two pathways that stimulate claudin expression; Hopx/Klf4 activation of Cldn4, 7 and 15, and Tcf7l2/Hnf4a upregulation of Cldn23. Chromatin Immunoprecipitation confirmed a Tcf7l2/Hnf4a/Claudin23 cascade. Hnf4a conditional knockout mice fail to induce Cldn23 during colonocyte differentiation.
2016-07-23 | GSE84742 | GEO
Project description:Analysis of the complex expression of claudin genes and transcription factors during intestinal epithelial cell differentiation across the crypt-to-surface colonic axis. Characterization of the complex expression gradients of transcription factors Hopx, Hnf4a, Klf4 and Tcfl2 and 12 claudin genes. In vitro confirmatory methods identified two pathways that stimulate claudin expression; Hopx/Klf4 activation of Cldn4, 7 and 15, and Tcf7l2/Hnf4a upregulation of Cldn23. Chromatin Immunoprecipitation confirmed a Tcf7l2/Hnf4a/Claudin23 cascade. Hnf4a conditional knockout mice fail to induce Cldn23 during colonocyte differentiation. The distal colon tissue was obtained from 4 male, 10-12 week old, C57BL/6 (WT) mice. The Arcturus Laser Capture Microdissection (LCM) system (Applied Biosystems/Life Technologies) was used to isolate crypt-base and surface cell populations providing two samples per mouse (crypt-base and surface). This resulted in 8 total samples for microarray analysis.
2016-07-23 | E-GEOD-84742 | biostudies-arrayexpress
Project description:The mucosal epithelium plays a key role in regulating immune homeostasis. Dysregulation of epithelial barrier function is associated with mucosal inflammation. Expression of claudin-2, a pore-forming tight junction protein, is highly upregulated during inflammatory bowel disease (IBD) and, due to its association with epithelial permeability, has been postulated to promote inflammation. Furthermore, claudin-2 also regulates colonic epithelial cell proliferation and intestinal nutrient absorption. However, the precise role of claudin-2 in regulating colonic epithelial and immune homeostasis remains unclear. Here, we demonstrate, using Villin-Claudin-2 transgenic (Cl-2TG) mice, that increased colonic claudin-2 expression unexpectedly protects mice against experimentally induced colitis and colitis-associated cancer. Notably, Cl-2TG mice exhibited increased colon length and permeability as compared with wild type (WT) littermates. However, despite their leaky colon, Cl-2TG mice subjected to experimental colitis were immune compromised, with reduced induction of TLR-2, TLR-4, Myd-88 expression and NF-kB and STAT3 activation. Most importantly, colonic macrophages in Cl-2TG mice exhibited an anergic phenotype. Claudin-2 overexpression also increased colonocyte proliferation and provided protection against colitis-induced colonocyte death. Taken together, our findings have revealed a critical role of claudin-2 in regulating colonic homeostasis, suggesting novel therapeutic strategies for inflammatory conditions of the gastrointestinal tract. 8-10 weeks old male Villin-Claudin-2 transgenic mice and WT littermates were provided either normal drinking water (control) or Dextran Sodium Sulfate (DSS: 4% w/v) for 10 days. 3 replicates each.
2013-09-15 | E-GEOD-46006 | biostudies-arrayexpress
Project description:The mucosal epithelium plays a key role in regulating immune homeostasis. Dysregulation of epithelial barrier function is associated with mucosal inflammation. Expression of claudin-2, a pore-forming tight junction protein, is highly upregulated during inflammatory bowel disease (IBD) and, due to its association with epithelial permeability, has been postulated to promote inflammation. Furthermore, claudin-2 also regulates colonic epithelial cell proliferation and intestinal nutrient absorption. However, the precise role of claudin-2 in regulating colonic epithelial and immune homeostasis remains unclear. Here, we demonstrate, using Villin-Claudin-2 transgenic (Cl-2TG) mice, that increased colonic claudin-2 expression unexpectedly protects mice against experimentally induced colitis and colitis-associated cancer. Notably, Cl-2TG mice exhibited increased colon length and permeability as compared with wild type (WT) littermates. However, despite their leaky colon, Cl-2TG mice subjected to experimental colitis were immune compromised, with reduced induction of TLR-2, TLR-4, Myd-88 expression and NF-kB and STAT3 activation. Most importantly, colonic macrophages in Cl-2TG mice exhibited an anergic phenotype. Claudin-2 overexpression also increased colonocyte proliferation and provided protection against colitis-induced colonocyte death. Taken together, our findings have revealed a critical role of claudin-2 in regulating colonic homeostasis, suggesting novel therapeutic strategies for inflammatory conditions of the gastrointestinal tract.
2013-09-15 | GSE46006 | GEO
Project description:Colonic epithelial cells facilitate host-microbe interactions to control mucosal immunity, and they also coordinate recycling and forming the mucus barrier. Epithelial barrier breakdown underpins inflammatory bowel disease (IBD). However, we do not know the specific contributions of each epithelial cell subtype to this process. Here, we profiled single colonic epithelial cells in health and IBD. Our results identified previously unknown subtypes and crypt gradients of progenitors, colonocytes and goblet cells. We also revealed a novel specialized metal ion storage and chloride secretory cell. In IBD, we discovered a unique cluster of disease associated goblet cells that remodels the barrier. We found downregulated WFDC2, a novel goblet cell expressing anti-protease that inhibited bacterial growth. Our in vivo studies demonstrated WFDC2 preserved tight junction integrity and prevented commensal invasion and mucosal inflammation. We delineate markers and transcriptional states, identify a new colonic epithelial cell and uncover fundamental principles of epithelial plasticity and barrier breakdown in IBD. Thus, our study reveals new therapeutic targets and disease-related mechanisms in IBD
2019-02-16 | PXD011655 | Pride
Project description:Background & Aims: HNF4α is an important transcriptional regulator of hepatocyte and pancreatic function. Hnf4α deletion is embryonically lethal with severe defects in visceral endoderm formation, liver maturation and colon development. However, the precise role of this transcription factor in maintaining homeostasis of the adult intestine remains unclear. Herein, we aimed to elucidate the adult intestinal functions of Hnf4α. Methods: A conditional intestinal epithelial Hnf4α knockout mouse was generated. Histological abnormality of the colonic mucosa was assessed by immunodetection and Western. Changes in global gene expression and biological network were analyzed. Results: Hnf4α intestine null mice developed normally until reaching young adulthood. Crypt distortion became apparent in the Hnf4α null colon at 3 months of age followed by focal areas of crypt dropout, increased immune cell infiltrates, crypt hyperplasia and early signs of polyposis later in life. A gene profiling analysis identified cell death and cell cycle related to cancer as the most significant sets of genes altered in the Hnf4α colon null mice. Expression levels of the tight junction proteins claudin 4, 8 and 15 were altered early in the colon epithelium of Hnf4α mutants and correlated with increased barrier permeability to a molecular tracer that does not normally penetrate normal mucosa. Conclusion: These observations support a functional role for Hnf4α in protecting the colonic mucosa against the initiation of the changes resembling inflammatory bowel diseases and polyp formation. Experiment Overall Design: HNF4alpha was conditionally knockout in the mouse epithelial colon with the villin CRE. A total of 3 control and 3 mutant littermates individuals were sacrificed at 1 year of age. The colon was harvested and Total RNA was isolated from each individuals. Each RNA sample was independently used to generate probes to screen affymetrix chips.
2009-01-13 | E-GEOD-11759 | biostudies-arrayexpress
Project description:Background & Aims: HNF4α is an important transcriptional regulator of hepatocyte and pancreatic function. Hnf4α deletion is embryonically lethal with severe defects in visceral endoderm formation, liver maturation and colon development. However, the precise role of this transcription factor in maintaining homeostasis of the adult intestine remains unclear. Herein, we aimed to elucidate the adult intestinal functions of Hnf4α. Methods: A conditional intestinal epithelial Hnf4α knockout mouse was generated. Histological abnormality of the colonic mucosa was assessed by immunodetection and Western. Changes in global gene expression and biological network were analyzed. Results: Hnf4α intestine null mice developed normally until reaching young adulthood. Crypt distortion became apparent in the Hnf4α null colon at 3 months of age followed by focal areas of crypt dropout, increased immune cell infiltrates, crypt hyperplasia and early signs of polyposis later in life. A gene profiling analysis identified cell death and cell cycle related to cancer as the most significant sets of genes altered in the Hnf4α colon null mice. Expression levels of the tight junction proteins claudin 4, 8 and 15 were altered early in the colon epithelium of Hnf4α mutants and correlated with increased barrier permeability to a molecular tracer that does not normally penetrate normal mucosa. Conclusion: These observations support a functional role for Hnf4α in protecting the colonic mucosa against the initiation of the changes resembling inflammatory bowel diseases and polyp formation.
2008-12-01 | GSE11759 | GEO
Project description:The early phase of colonic epithelial wound healing involves cellular reprogramming to a fetal-like state and reorganization of discrete crypt units into merged wound channels. After re-epithelialization is complete, a latter phase restoring homeostatic signaling and crypt patterning must occur. However, the signals that mediate this regenerative transition are unknown. Here we show that injury-associated upregulation of a cytokine receptor, tumor necrosis factor (TNF) receptor 2 (R2, TNFR2, Tnfrsf1b), suppresses fetal-like signaling and promotes crypt production. We used tissue clearing and whole-mount imaging, RNA-Seq, and organoid cultures to characterize mice with a colonic epithelial-specific deletion of TNFR2. These mice exhibited increased crypt size and reduced fission in adult homeostasis and after colitis, abnormal persistence of fetal-like molecular markers in organoids and after injury, reduced terminal differentiation, and increased proliferative potential. These results demonstrate how epithelial cells can adapt to inflammatory cues to regulate wound healing morphogenesis and signaling.
2023-08-22 | GSE157751 | GEO
Project description:Background and Aims: HNF4? is a nuclear hormone receptor transcription factor that has been shown to be required for hepatocyte differentiation and development of the liver. It has also been implicated in regulating expression of genes that act in the epithelium of the lower gastrointestinal tract. This implied that HNF4? might be required for development of the gut. Methods: We generated mouse embryos in which Hnf4? was ablated in the epithelial cells of the fetal colon using Cre-loxP technology. Embryos were examined using a combination of histology, immunohistochemistry, gene array and RT-PCR, and chromatin immunoprecipitation analyses to define the consequence of loss of HNF4? on colon development. Results: Embryos could be generated until E18.5 that lacked HNF4? in their colon. Although, early stages of colonic development occurred, HNF4? null colons failed to form normal crypts. In addition, goblet cell maturation was perturbed and expression of an array of genes that encode proteins with diverse roles in colon function was disrupted. Several genes whose expression in the colon was dependent on HNF4? contained HNF4?âbinding sites sequences within putative transcriptional regulatory regions and a subset of these sites were occupied by HNF4? in vivo. Conclusion: HNF4? is a transcription factor that is essential for development of the mammalian colon, regulates goblet cell maturation and is required for expression of genes that control normal colon function and epithelial cell differentiation. Experiment Overall Design: COMPARISON OF 3 MUTANT TO 2 CONTROL COLONS.
2008-06-12 | E-GEOD-3116 | biostudies-arrayexpress
Project description:Functions of Ascl2 in colonic stem cell maintenance and regeneration. We used RNA-sequencing to profile gene expression in regenerating crypt cells and Ascl2-deficient colonic stem cells, and ASCL2 ChIP-seq to identify transcriptional target genes.
2020-01-17 | GSE130822 | GEO