Similar Datasets
Project description:In this experiment we analyse Mtg16 binding to chromatin in isolated mouse intestinal crypts from VillinCreER, Rbpjfl/fl mice 4 days following TM induction (Notch inhibition).
2020-06-17 | GSE124184 | GEO
Project description:In this experiment, the differential gene expression was examined in intestinal epithelial cells of Mtg16 null mice compared to wild type.
2020-06-17 | GSE124185 | GEO
Project description:Co-repressors Mtg8 and Mtg16 regulate niche exit and early fate decision of crypt stem cells
| PRJNA510964 | ENA
Project description:Co-repressors Mtg8 and Mtg16 regulate niche exit and early fate decision of crypt stem cells (RNA-seq)
| PRJNA510966 | ENA
Project description:Co-repressors Mtg8 and Mtg16 regulate niche exit and early fate decision of crypt stem cells (ChIP-seq)
| PRJNA510965 | ENA
Project description:Background & aimsNotch signaling maintains intestinal stem cells (ISCs). When ISCs exit the niche, Notch signaling among early progenitor cells at position +4/5 regulates their specification toward secretory vs enterocyte lineages (binary fate). The transcription factor ATOH1 is repressed by Notch in ISCs; its de-repression, when Notch is inactivated, drives progenitor cells to differentiate along the secretory lineage. However, it is not clear what promotes transition of ISCs to progenitors and how this fate decision is established.MethodsWe sorted cells from Lgr5-GFP knockin intestines from mice and characterized gene expression patterns. We analyzed Notch regulation by examining expression profiles (by quantitative reverse transcription polymerase chain reaction and RNAscope) of small intestinal organoids incubated with the Notch inhibitor DAPT, intestine tissues from mice given injections of the γ-secretase inhibitor dibenzazepine, and mice with intestine-specific disruption of Rbpj. We analyzed intestine tissues from mice with disruption of the RUNX1 translocation partner 1 gene (Runx1t1, also called Mtg8) or CBFA2/RUNX1 partner transcriptional co-repressor 3 (Cbfa2t3, also called Mtg16), and derived their organoids, by histology, immunohistochemistry, and RNA sequencing (RNA-seq). We performed chromatin immunoprecipitation and sequencing analyses of intestinal crypts to identify genes regulated by MTG16.ResultsThe transcription co-repressors MTG8 and MTG16 were highly expressed by +4/5 early progenitors, compared with other cells along crypt-villus axis. Expression of MTG8 and MTG16 were repressed by Notch signaling via ATOH1 in organoids and intestine tissues from mice. MTG8- and MTG16-knockout intestines had increased crypt hyperproliferation and expansion of ISCs, but enterocyte differentiation was impaired, based on loss of enterocyte markers and functions. Chromatin immunoprecipitation and sequencing analyses showed that MTG16 bound to promoters of genes that are specifically expressed by stem cells (such as Lgr5 and Ascl2) and repressed their transcription. MTG16 also bound to previously reported enhancer regions of genes regulated by ATOH1, including genes that encode Delta-like canonical Notch ligand and other secretory-specific transcription factors.ConclusionsIn intestine tissues of mice and human intestinal organoids, MTG8 and MTG16 repress transcription in the earliest progenitor cells to promote exit of ISCs from their niche (niche exit) and control the binary fate decision (secretory vs enterocyte lineage) by repressing genes regulated by ATOH1.
| S-EPMC7607384 | biostudies-literature
Project description:In the mammalian intestine, crypts of Leiberkühn house intestinal epithelial stem /progenitor cells at their base. We found that the presence of this structure was supported by the physiologic role of a prominent bacterial metabolite, butyrate. This bacterially-produced short chain fatty acid inhibited intestinal epithelial proliferation at physiologic concentrations. During homeostasis, butyrate did not suppress epithelial stem proliferation because it was metabolized by differentiated colonocytes. Provision of butyrate access to stem/progenitor cells either through mucosal injury or application to a crypt-less host led to inhibition of proliferation. The mechanism was dependent on HDAC inhibition in stem cells and the transcription factor Foxo3. Thus, the mammalian crypt unit structure provides energy for differentiated cells at a distance from the crypt base and this action prevents suppression of stem/progenitor proliferation. In total 4 samples were analyzed from 2 independent experiments. Two samples of colonic stem cells treated with 1mM Butyrate and two samples of colonic stem cells treated with 1mM NaCl (mock) as a control
2016-06-27 | E-GEOD-74601 | biostudies-arrayexpress
Project description:Central to the ABCE model of flower development is the antagonistic interaction between class A and class C genes. The molecular mechanisms underlying the A-C antagonism are not completely understood. In Arabidopsis thaliana, miR172 is expressed in the inner floral whorls where it downregulates the class A gene APETALA 2 (AP2). However, what controls this predominantly inner whorl-specific expression of miR172 is not known. We show that the LEUNIG (LUG) and SEUSS (SEU) co-repressors repress miR172 expression in the outer whorls of A. thaliana flowers. The recruitment of LUG/SEU to the miR172 promoters is dependent on AP2, suggesting that AP2 represses the expression of its cognate microRNA. Our study provides new insights into the molecular mechanisms underlying the A-C antagonism and shed light on the transcriptional regulation of miR172 during flower development.
| S-EPMC4074289 | biostudies-literature
Project description:In the mammalian intestine, crypts of Leiberkühn house intestinal epithelial stem /progenitor cells at their base. We found that the presence of this structure was supported by the physiologic role of a prominent bacterial metabolite, butyrate. This bacterially-produced short chain fatty acid inhibited intestinal epithelial proliferation at physiologic concentrations. During homeostasis, butyrate did not suppress epithelial stem proliferation because it was metabolized by differentiated colonocytes. Provision of butyrate access to stem/progenitor cells either through mucosal injury or application to a crypt-less host led to inhibition of proliferation. The mechanism was dependent on HDAC inhibition in stem cells and the transcription factor Foxo3. Thus, the mammalian crypt unit structure provides energy for differentiated cells at a distance from the crypt base and this action prevents suppression of stem/progenitor proliferation.
2016-06-27 | GSE74601 | GEO
Project description:Cycling Lgr5+ stem cells fuel the rapid turnover of the adult intestinal epithelium. The existence of quiescent Lgr5+ cells has been reported, while an alternative quiescent stem cell population is believed to reside at crypt position +4. Here, we generated a novel Ki67RFP knock-in allele that identifies dividing cells. Using Lgr5-GFP;Ki67RFP mice, we isolated crypt stem and progenitor cells with distinct Wnt signaling levels and cell cycle features and generated their molecular signature using microarrays. Stem cell potential of these populations was further characterized using the intestinal organoid culture. We found that Lgr5high stem cells are continuously in cell cycle, while a fraction of Lgr5low progenitors that reside predominantly at +4 position exit the cell cycle. Unlike fast dividing CBCs, Lgr5low Ki67- cells have lost their ability to initiate organoid cultures, are enriched in secretory differentiation factors, and resemble the Dll1 secretory precursors and the label-retaining cells of Winton and colleagues. Our findings support the cycling stem cell hypothesis and highlight the cell cycle heterogeneity of early progenitors during lineage commitment.
| S-EPMC4195772 | biostudies-literature