Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA322496 | ENA |
REPOSITORIES: ENA
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Project description:Intronic polyadenylation of PDGFRα in resident stem cells attenuates muscle fibrosis
| PRJNA257474 | ENA
Project description:The platelet-derived growth factor receptor alpha (PDGFRα) exhibits divergent effects in skeletal muscle. At physiological levels, signaling through this receptor promotes muscle development in growing embryos and proper angiogenesis in regenerating adult muscle. However, either increased PDGF ligands or enhanced PDGFRα pathway activity causes pathological fibrosis. This excessive collagen deposition, which is seen in aged and diseased muscle, interferes with proper muscle function and limits the effectiveness of gene- and cell-based therapies for muscle disorders. Although compelling evidence exists for the role of PDGFRα in fibrosis, little is known about the cells through which this pathway acts. Here we show that PDGFRα signaling regulates a population of muscle-resident fibro/adipogenic progenitors (FAPs) that play a supportive role in muscle regeneration but may also cause fibrosis when aberrantly regulated. We found that FAPs produce multiple transcriptional variants of PDGFRα with different polyadenylation sites, including an intronic variant that codes for a protein isoform containing a truncated kinase domain. This variant, upregulated during regeneration, acts as a decoy to inhibit PDGF signaling and to prevent FAP over-activation. Moreover, increasing expression of this isoform limits fibrosis in vivo, suggesting both biological relevance and therapeutic potential of modulating polyadenylation patterns in stem cell populations. We used microarrays to explore the biological effects of altering intronic polyadenylation of PDGFRα in FAPs.
2016-11-30 | GSE60099 | GEO
Project description:The platelet-derived growth factor receptor alpha (PDGFRα) exhibits divergent effects in skeletal muscle. At physiological levels, signaling through this receptor promotes muscle development in growing embryos and proper angiogenesis in regenerating adult muscle. However, either increased PDGF ligands or enhanced PDGFRα pathway activity causes pathological fibrosis. This excessive collagen deposition, which is seen in aged and diseased muscle, interferes with proper muscle function and limits the effectiveness of gene- and cell-based therapies for muscle disorders. Although compelling evidence exists for the role of PDGFRα in fibrosis, little is known about the cells through which this pathway acts. Here we show that PDGFRα signaling regulates a population of muscle-resident fibro/adipogenic progenitors (FAPs) that play a supportive role in muscle regeneration but may also cause fibrosis when aberrantly regulated. We found that FAPs produce multiple transcriptional variants of PDGFRα with different polyadenylation sites, including an intronic variant that codes for a protein isoform containing a truncated kinase domain. This variant, upregulated during regeneration, acts as a decoy to inhibit PDGF signaling and to prevent FAP over-activation. Moreover, increasing expression of this isoform limits fibrosis in vivo, suggesting both biological relevance and therapeutic potential of modulating polyadenylation patterns in stem cell populations. We used microarrays to explore the biological effects of altering intronic polyadenylation of PDGFRα in FAPs in vivo.
2016-11-30 | GSE81744 | GEO
Project description:Tissue-resident PDGFRα stromal cells modulate both fibrosis and tissue revascularization during wound repair
| PRJNA395942 | ENA
Project description:SILAC based protein correlation profiling using size exclusion of protein complexes derived from Mus musculus tissues (Heart, Liver, Lung, Kidney, Skeletal Muscle, Thymus)
2021-05-05 | PXD022309 | Pride
Project description:SILAC based protein correlation profiling using size exclusion of protein complexes derived from seven Mus musculus tissues (Heart, Brain, Liver, Lung, Kidney, Skeletal Muscle, Thymus)
2018-04-24 | PXD007288 | Pride
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: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:PDGFRα+ cells are interstitial/perivascular mesenchymal progenitor cells that have been associated with fibro-adipogenic processes. However, their function during tissue homeostasis or in response to revascularization and regeneration stimuli remains to be fully defined. Here, by high-throughput transcriptomic analysis, adoptive transfer and multicolor lineage tracking we showed that PDGFRα+ cells from skeletal muscle cluster as a population that is transcriptionally distinct from other mesenchymal stromal cells and with an essential role in tissue revascularization and restructuring of ischemic areas. We further showed that tissue regeneration involves the removal of differentiated PDGFRα+-derived cells, while pathological healing occurred if PDGFRα+-derived cells persisted as terminally differentiated mesenchymal cells (e.g. myofibroblasts). From the perspective of tissue regeneration, these studies support a context-dependent 'yin-yang' biology of PDGFRα+ cells, that possess an innate ability to stabilize newly formed blood vessels and concurrently limit injury expansion after ischemia, while also being capable of promoting fibrosis in an unfavorable environment.
2019-07-01 | GSE101930 | GEO