Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA328081 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Paneth cells are a highly specialized population of intestinal epithelial cells located in the crypt adjacent to Lgr5+ stem cells, from which they differentiate through a process that requires downregulation of the Notch pathway. Their ability to store and release antimicrobial peptides protects the host from intestinal pathogens and controls intestinal inflammation. Here we show that PKCλ/ι is required for Paneth cell differentiation at the level of Atoh1 and Gfi1, through the control of EZH2 stability by direct phosphorylation. The selective inactivation of PKCλ/ι in epithelial cells results in the loss of mature Paneth cells, increased apoptosis and inflammation, and enhanced tumorigenesis. Importantly, PKCλ/ι expression in human Paneth cells decreases with progression of Crohn's disease. Kaplan-Meier survival analysis of CRC patients revealed that low PRKCI levels correlated with significantly worse patient survival. Therefore, PKCλ/ι is a negative regulator of intestinal inflammation and cancer through its role in Paneth cell homeostasis.
2017-08-23 | GSE84118 | GEO
Project description:Cellular metabolism is emerging as a potent regulator of cell fate, raising the possibility that the recently discovered metabolic heterogeneity between newly synthesized and chronologically old organelles may impact stem cell fate in mammalian tissues. The small intestine is maintained by actively cycling intestinal stem cells (ISCs) that give rise to metabolically distinct progeny, including their Paneth cell niche. Here, we find that asymmetric cell division generates a subset of ISCs enriched for old mitochondria (ISCmito-O). Although ISCmito-O lack characteristics of reserve stem cells, they form organoids niche-independently, owing to their ability to recreate the Paneth cell niche. Mechanistically, mitochondria in ISCmito-O generate more alpha-ketoglutarate (aKG), driving ten-eleven translocation (Tet) methylcytosine dioxygenase-mediated epigenetic changes that are associated with differentiation towards the Paneth cell fate. aKG supplementation in vivo promotes Paneth cell turnover leading to niche renewal, which promotes recovery from chemotherapy-induced damage in aged animals. Our results reveal a subpopulation of intestinal stem cells whose old mitochondria metabolically regulate cell fate, and provide proof-of-principle for metabolically promoted replacement of specific aged cell types in vivo.
2025-04-24 | MTBLS12349 | MetaboLights
Project description:The experiment aims to analyze the differences in expressed genes in Paneth cells upon acute intestinal inflammation compared to Paneth cells from non-inflamed control mice
2018-07-18 | GSE117216 | GEO
Project description:Cellular binary fate decisions require the progeny to silence genes associated with the alternative fate. The major subsets of alpha:beta T cells have been extensively studied as a model system for fate decisions. While the transcription factor RUNX3 is required for the initiation of Cd4 silencing in CD8 T cell progenitors, it is not required to maintain the silencing of Cd4 and other helper T lineage genes. The other runt domain containing protein, RUNX1, silences Cd4 in an earlier T cell progenitor, but this silencing is reversed whereas the gene silencing after RUNX3 expression is not reverse. Therefore, we hypothesized that RUNX3 and not RUNX1 recruits other factors that maintains the silencing of helper T lineage genes in CD8 T cells. To this end, we performed a proteomics screen of RUNX1 and RUNX3 to determine candidate silencing factors.
2019-11-12 | PXD007511 | Pride
Project description:Impact of intestinal colonization on Paneth cell gene expression
| PRJNA96567 | ENA
Project description: Not available
| S-EPMC8784167 | biostudies-literature
Project description:Paneth cells, intestine-originated innate immune-like cells, are important for maintenance of the intestinal stem cell niche, gut microbiota, and gastrointestinal barrier. Dysfunctional Paneth cells under pathological conditions are a site of origin for intestinal inflammation. However, mechanisms underlying stress-induced Paneth cell dysregulation remains unclear. We have previously reported that deletion of SIRT1 in the intestinal epithelium (SIRT1 iKO) leads to hyperaction of Paneth cells along with an increased sensitivity to Dextran sodium sulfate (DSS)-induced colitis. We recently generated a Paneth-cell specific SIRT1 KO mouse model (SIRT1 PKO). Similar to mice with SIRT1 iKO mice, SIRT1 PKO mice had increased abundance as well as hyperactivation of Paneth cells in vivo and in cultured intestinal organoids. However, in contrast to the hypersensitivity of SIRT1 iKO mice to chemical- or age-induced inflammation, SIRT1 PKO mice were protected from Dextran sodium sulfate (DSS)-colitis.
2025-03-31 | GSE262546 | GEO
Project description: Not available
| S-EPMC11335981 | biostudies-literature
Project description:Intestinal epithelial homeostasis is maintained by a complex interplay between different epithelial cells, gut microorganisms, and immune cells. Disruption of this interplay contributes to inflammatory and immune diseases associated with gut microbiome dysbiosis. A genetic factor that modulates the interactions between gut epithelium, microbiota and immune cells is sirtuin 1 (SIRT1), the most conserved mammalian NAD+-dependent protein deacetylase. We and others have shown that deficiency of intestinal epithelial SIRT1 leads to intestinal inflammation, disruption of gut microbial composition, and altered susceptibility to environmentally induced colitis. Recently we generated a Paneth-cell specific SIRT1 KO mouse model (SIRT1 PKO). Similar to mice with SIRT1 deficiency in whole intestinal epithelium, SIRT1 PKO mice had increased abundance as well as hyperactivation of Paneth cells in vivo and in cultured intestinal organoids. Single-cell RNA-seq of whole intestinal cell populations confirmed that deletion of Paneth cell SIRT1 significantly increases the abundance of Paneth cells. This increase was accompanied with an elevated abundance of intestinal stem cells, transition amplifying cells, and enterocytes. Consistently, SIRT1 PKO mice were able to better maintain their intestinal epithelial integrity during aging and were protected from chemically induced colitis compared to control mice. Deletion of SIRT1 in Paneth cells further induced profound alterations in gut microbiota. Using microbiota-depleted mice and fecal transplantation, we demonstrate that Paneth cell SIRT1 deficiency ameliorates colitis through the gut microbiota. Collectively, our findings uncover an unanticipated function of Paneth cell SIRT1 in conferring sensitivity of the gut epithelium to stress.
2026-01-20 | GSE261216 | GEO
Project description: Not available
| S-EPMC4490682 | biostudies-literature