Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA328081 | ENA |
REPOSITORIES: ENA
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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:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
| 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:Translational research is commonly performed in the C57B6/J mouse strain, chosen for its genetic homogeneity and phenotypic uniformity. Here, we evaluate the suitability of the white-footed deer mouse (Peromyscus leucopus) as a model organism for aging research, offering a comparative analysis against C57B6/J and diversity outbred (DO) Mus musculus strains. Our study includes comparisons of body composition, skeletal muscle function, and cardiovascular parameters, shedding light on potential applications and limitations of P. leucopus in aging studies. Notably, P. leucopus exhibits distinct body composition characteristics, emphasizing reduced muscle force exertion and a unique metabolism, particularly in fat mass. Cardiovascular assessments showed changes in arterial stiffness, challenging conventional assumptions and highlighting the need for a nuanced interpretation of aging-related phenotypes. Our study also highlights inherent challenges associated with maintaining and phenotyping P. leucopus cohorts. Behavioral considerations, including anxiety-induced responses during handling and phenotyping assessment, pose obstacles in acquiring meaningful data. Moreover, the unique anatomy of P. leucopus necessitates careful adaptation of protocols designed for Mus musculus. While showcasing potential benefits, further extensive analyses across broader age ranges and larger cohorts are necessary to establish the reliability of P. leucopus as a robust and translatable model for aging studies.
| 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:BackgroundCopy number variation is an important dimension of genetic diversity and has implications in development and disease. As an important model organism, the mouse is a prime candidate for copy number variant (CNV) characterization, but this has yet to be completed for a large sample size. Here we report CNV analysis of publicly available, high-density microarray data files for 351 mouse tail samples, including 290 mice that had not been characterized for CNVs previously.ResultsWe found 9634 putative autosomal CNVs across the samples affecting 6.87% of the mouse reference genome. We find significant differences in the degree of CNV uniqueness (single sample occurrence) and the nature of CNV-gene overlap between wild-caught mice and classical laboratory strains. CNV-gene overlap was associated with lipid metabolism, pheromone response and olfaction compared to immunity, carbohydrate metabolism and amino-acid metabolism for wild-caught mice and classical laboratory strains, respectively. Using two subspecies of wild-caught Mus musculus, we identified putative CNVs unique to those subspecies and show this diversity is better captured by wild-derived laboratory strains than by the classical laboratory strains. A total of 9 genic copy number variable regions (CNVRs) were selected for experimental confirmation by droplet digital PCR (ddPCR).ConclusionThe analysis we present is a comprehensive, genome-wide analysis of CNVs in Mus musculus, which increases the number of known variants in the species and will accelerate the identification of novel variants in future studies.
| S-EPMC4490682 | biostudies-literature