DNA methylation is required for the control of stem cell differentiation in the small intestine
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ABSTRACT:
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR454963.fastq.gz | Fastqsanger.gz | |||
| ERR454964_1.fastq.gz | Fastqsanger.gz | |||
| ERR454964_2.fastq.gz | Fastqsanger.gz | |||
| ERR454965_1.fastq.gz | Fastqsanger.gz | |||
| ERR454965_2.fastq.gz | Fastqsanger.gz |
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Project description:The mammalian intestinal epithelium has a unique organization in which crypts harboring stem cells produce progenitors and finally clonal populations of differentiated cells. Remarkably, the epithelium is replaced every 3-5 d throughout adult life. Disrupted maintenance of the intricate balance of proliferation and differentiation leads to loss of epithelial integrity or barrier function or to cancer. There is a tight correlation between the epigenetic status of genes and expression changes during differentiation; however, the mechanism of how changes in DNA methylation direct gene expression and the progression from stem cells to their differentiated descendants is unclear. Using conditional gene ablation of the maintenance methyltransferase Dnmt1, we demonstrate that reducing DNA methylation causes intestinal crypt expansion in vivo. Determination of the base-resolution DNA methylome in intestinal stem cells and their differentiated descendants shows that DNA methylation is dynamic at enhancers, which are often associated with genes important for both stem cell maintenance and differentiation. We establish that the loss of DNA methylation at intestinal stem cell gene enhancers causes inappropriate gene expression and delayed differentiation.
| S-EPMC3967052 | biostudies-literature
Project description:Age and Human small intestine Metagenome
| PRJNA715766 | ENA
Project description:Aim: The mammalian gut is the largest endocrine organ. Dozens of hormones secreted by enteroendocrine cells regulate a variety of physiological functions of the gut but also of the pancreas and brain. Here, we examined the role of the helix-loop-helix transcription factor ID2 during the differentiation of intestinal stem cells along the enteroendocrine lineage. Methods: To assess the functions of ID2 in the adult mouse small intestine, we used single-cell RNA sequencing, genetically modified mice, and organoid assays. Results: We found that in the adult intestinal epithelium Id2 is predominantly expressed in enterochromaffin and peptidergic enteroendocrine cells. Consistently, the loss of Id2 leads to the reduction of Chromogranin A-positive enteroendocrine cells. In contrast, the numbers of tuft cells are increased in Id2 mutant small intestine. Moreover, ablation of Id2 elevates the numbers of Serotonin+ enterochromaffin cells and Ghrelin+ X-cells in the posterior part of the small intestine. Finally, Id2 acts downstream of BMP signalling during the differentiation of Glucagon Like Peptide-1+ L-cells and Cholecystokinin+ I-cells towards Neurotensin+PYY+ N-cells. Conclusion: Id2 plays an important role in cell fate decisions in the adult small intestine. Firstly, ID2 suppresses the differentiation of secretory intestinal epithelial progenitors towards tuft cell lineage and thus controls host immune response on commensal and parasitic microbiota. Next, ID2 is essential for establishing a differentiation gradient for enterochromaffin and X-cells along the anterior-posterior axis of the gut. Finally, ID2 is necessary for the differentiation of N-cells thus ensuring a differentiation gradient along the crypt-villi axis.
2022-06-21 | GSE178586 | GEO
Project description:The mammalian intestinal epithelium has a unique organization where crypts harboring stem cells produce progenitors and finally clonal populations of differentiated cells. Remarkably, the epithelium is replaced every three to five days throughout adult life. Disrupted maintenance of the intricate balance of proliferation and differentiation leads to loss of epithelial integrity, barrier function, or cancer. There is a tight correlation between epigenetic status of genes and expression changes during differentiation; however, the mechanism of how changes in DNA methylation direct gene expression and the progression from stem cells to their differentiated descendants is unclear. Using conditional gene ablation of the maintenance methyltransferase Dnmt1, we demonstrate that reducing DNA methylation causes intestinal crypt expansion in vivo. Determination of the base-resolution DNA methylome in stem cells and their differentiated descendants shows that DNA methylation is dynamic at enhancers, which are often associated with genes important for both stem cell maintenance and differentiation. We establish that the loss of DNA methylation at intestinal stem cell gene enhancers causes inappropriate gene expression and delayed differentiation.
2014-03-13 | E-MTAB-2350 | biostudies-arrayexpress
Project description:ID2 controls differentiation of entero-endocrine cells in mouse small intestine
| PRJNA739693 | ENA
Project description:The intestine is composed of an epithelial layer, containing rapidly proliferating cells that mature into two distinct anatomic regions, the small and the large intestine. Although previous studies have identified stem cells as the cell-of-origin for the whole intestine, no studies have compared stem cells derived from the small and large intestine. Here, we report intrinsic differences between these two populations of cells. Primary epithelial cells isolated from human fetal small and large intestine and expanded with Wnt agonist, R-spondin 2, displayed differential expression of stem cell markers and separate hierarchical clustering of gene expression involved in differentiation, proliferation and disease pathways. Using a three-dimensional in vitro differentiation assay, single cells derived from small and large intestine formed distinct organoid architecture with cellular hierarchy similar to that found in primary tissue. Our characterization of human fetal intestinal stem cells defies the classical definition proposed by most where small and large intestine are repopulated by an identical epithelial stem cell and raises the question of the importance of intrinsic and extrinsic cues in the development of intestinal diseases. 12 samples were analyzed. They consisted of human fetal small and large intestine (SI; n=6 and LI; n=6) stem cells, expanded with Wnt agonist and R-spondin 2. Differential expression of genes in epithelial cells from both the large and small intestine were observed.
2015-01-15 | E-GEOD-56525 | biostudies-arrayexpress
Project description:The intestine is composed of an epithelial layer, containing rapidly proliferating cells that mature into two distinct anatomic regions, the small and the large intestine. Although previous studies have identified stem cells as the cell-of-origin for the whole intestine, no studies have compared stem cells derived from the small and large intestine. Here, we report intrinsic differences between these two populations of cells. Primary epithelial cells isolated from human fetal small and large intestine and expanded with Wnt agonist, R-spondin 2, displayed differential expression of stem cell markers and separate hierarchical clustering of gene expression involved in differentiation, proliferation and disease pathways. Using a three-dimensional in vitro differentiation assay, single cells derived from small and large intestine formed distinct organoid architecture with cellular hierarchy similar to that found in primary tissue. Our characterization of human fetal intestinal stem cells defies the classical definition proposed by most where small and large intestine are repopulated by an identical epithelial stem cell and raises the question of the importance of intrinsic and extrinsic cues in the development of intestinal diseases.
2015-01-15 | GSE56525 | GEO
Project description:Human small intestine metagenome in smokers, ex-smokers and non-smokers
| PRJNA732897 | ENA
Project description:To define changes in gene expression resulting from loss of hnf4 in the small intestine. Keywords: genetic modification
2005-12-31 | GSE3124 | GEO