Crosstalk between macrophages and fibro-adipogenic progenitors during muscle regeneration
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA726154 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The purpose of this study is to investigate how melatonin-influenced promyogenic factor secreted from fibro-adipogenic progenitors (FAPs) regulate muscle regeneration and muscle cell fusion during muscle repair. We highlighted the role of melatonin in regulating crosstalk between muscle stem cells and FAPs during muscle regeneration. Mice that were treated with melatonin exhibited improved muscle regeneration and reduced intramuscular fat deposition, which were associated with enhanced myogenesis, remodeled lipid metabolism and reduced immune cell infiltration. Notably, melatonin did not exert positive effects on cell fusion and myotube formation during differentiation. Interestingly, melatonin repressed fibro-adipogenic progenitor (FAP) adipogenesis in a dose-dependent manner in vitro. Furthermore, melatonin treatment enhanced the pro-myogenic effects of FAPs, which stimulated GDF10 secretion to promote muscle cell fusion and induce myotube hypertrophy.
2023-06-30 | GSE214008 | GEO
Project description:Fibro/adipogenic progenitors were isolated and treated by Musclin for 48 hours in vitro.
2021-09-14 | PXD028468 |
Project description:The purpose of this study is to investigate how immune cells (macrophages) are closely linked with fibro-adipogenic progenitors (FAPs) during recovery processe. We report that the depletion of Mrc1+ (gene encoding CD206) M2-like macrophages promoted the recovery of muscle after injury. A total RNA sequence analysis of whole muscle or isolated FAPs revealed that the depletion of Mrc1+ M2-like macrophages resulted in the activation of FAPs. Activated FAPs secrete follistatin (Fst), a promyogenic factor, boosting the recovery process. We further determined that the knockdown of FAPs-derived Fst delayed the recovery process. Mechanistically, Mrc1+ M2-like macrophages-specific TGF-b1 inhibited the activation of FAPs, and the FAPs failed to secrete Fst.
2022-09-12 | GSE173555 | GEO
Project description:Fibro-adipogenic progenitors (FAPs) are emerging cellular components of the skeletal muscle regenerative environment. The alternative functional phenotype of FAPs - either supportive of muscle regeneration or promoting fibro-adipogenic degeneration - is a key determinant in the pathogenesis of muscular diseases, including Duchenne Muscular Dystrophy (DMD). However, the molecular regulation of FAPs is still unknown. We show here that an "HDAC-myomiR-BAF60 variant network" regulates the functional phenotype of FAPs in dystrophic muscles of mdx mice. Combinatorial analysis of gene expression microarray and genome-wide chromatin remodeling by Nuclease accessibility (NA)-seq revealed that HDAC inhibitors de-repress a "latent" myogenic program in FAPs from dystrophic muscles at early stages of disease progression. In these cells HDAC inhibition promoted the expression of two core components of the myogenic transcriptional machinery, MyoD and BAF60C, and upregulated the myomiRs (miRs) miR-1.2, miR-133 and miR-206, which target two alternative BAF60 variants (BAF60A and B) ultimately leading to the activation of a pro-myogenic program at the expense of the fibro-adipogenic phenotype. By contrast, FAPs from dystrophic muscles at late stages of disease progression displayed resistance to HDACi-induced chromatin remodeling at myogenic loci and fail to activate the pro-myogenic phenotype. These results reveal a previously unappreciated disease stage-specific bipotency of mesenchimal cells within the regenerative environment of dystrophic muscles. Resolution of such bi-potency by epigenetic interventions, such as HDACi, provides the molecular rationale for the in situ reprogramming of target cells to promote therapeutic regeneration of dystrophic muscles. miRNA modulation upon Histone Deacetylase inhibition in Fibro-Adipogenic Progenitors (FAPs) derived from young mdx mice was evaluated by small RNA-sequencing in 2 controls and 2 treated samples
2014-04-23 | E-GEOD-51933 | biostudies-arrayexpress
Project description:Fibro adipogenic progenitors (FAPs) promote satellite cell differentiation in adult skeletal muscle regeneration. However, in pathological conditions, FAPs are responsible for fibrosis and fatty infiltrations. Here we show that the NOTCH pathway negatively modulates FAP differentiation both in vitro and in vivo. However, FAPs isolated from young dystrophin- deficient mdx mice are insensitive to this control mechanism. An unbiased mass spectrometry-based proteomic analysis of FAPs from muscles of wild type and mdx mice, suggest that the synergistic cooperation between NOTCH and inflammatory signals controls FAP differentiation. Remarkably, we demonstrated that factors released by hematopoietic cells restore the sensitivity to NOTCH adipogenic inhibition in mdx FAPs. These results offer a basis for rationalizing pathological ectopic fat infiltrations in skeletal muscle and may suggest new therapeutic strategies to mitigate the detrimental effects of fat depositions in muscles of dystrophic patients.
2019-06-24 | PXD014195 | Pride
Project description:Musclin-resident fibro/adipogenic progenitors were isolated and treated by Musclin or vehicle for 48 hours in vitro. Then, the total proteome was analyzed.
2021-09-13 | PXD028469 |
Project description:Role of Prdm16 in fibro-adipogenic progenitors
| PRJNA624179 | ENA
Project description:We report the bulk RNA-seq of healthy and senescent mouse fibro-adipogenic progenitors (FAPs)
2024-01-11 | GSE247975 | GEO
Project description:The aim of this study is to explore the molecular mechanism on how Musclin regulates the biological process of fibro/adipogenic progenitors.
2022-09-15 | GSE184012 | GEO
Project description:In vertebrates, activation of innate immunity is an early response to injury, implicating it in the regenerative process. However, the mechanisms by which innate signals might regulate stem cell functionality are unknown. Here we demonstrate that type 2 innate immunity is required for regeneration of skeletal muscle after injury. Muscle damage results in rapid recruitment of eosinophils, which secrete IL-4 to activate the regenerative actions of muscle resident fibro/adipocyte progenitors (FAPs). In FAPs, IL-4/IL-13 signaling serves as a key switch to control their fate and functions. Activation of IL-4/IL-13 signaling promotes proliferation of FAPs to support myogenesis, while inhibiting their differentiation into adipocytes. Surprisingly, type 2 cytokine signaling is also required in FAPs, but not myeloid cells, for rapid clearance of necrotic debris, a process that is necessary for timely and complete regeneration of tissues. Fibroadipocyte progenitors were isolated from wild-type and IL-4Ra knockout (IL-4Ra -/-) mice and were treated with vehicle or IL4 stimulation in culture prior to microarray analysis. 4 biological replicates of each condition were performed.
2013-04-11 | E-GEOD-44933 | biostudies-arrayexpress