A myogenin+/CD74+ adult muscle stem cell population during regeneration of skeletal muscle lacking miR-501
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE200501 | GEO | 2023/03/21
REPOSITORIES: GEO
Similar Datasets
Project description:Adult muscle stem cells show a high transcriptional and clonal heterogeneity during ageing. Whether microRNAs contribute to this diversity is not known. Here we use global and tissue-specific genetic deletion of microRNA (miR)-501 that is highly enriched in activated myogenic progenitor cells 3 to address this question. Deletion of miR-501 reduced myofiber size and resilience of muscle fibers to injury and exercise in adult skeletal muscle. miR-501 elicits this effect by changing sarcomeric gene expression in newly built myofibers in vivo.
2023-03-16 | GSE199111 | GEO
Project description:A myogenin+/CD74+ adult muscle stem cell population during regeneration of skeletal muscle lacking miR-501
| PRJNA824836 | ENA
Project description:Skeletal muscle holds an intrinsic capability of growth and regeneration both in physiological conditions and in case of injury. Chronic muscle illnesses, generally caused by genetic and acquired factors, lead to deconditioning of the skeletal muscle structure and function, and are associated with a significant loss in muscle mass. At the same time, progressive muscle wasting is a hallmark of aging. Given the paracrine properties of myogenic stem cells, extracellular vesicle-derived signals have been studied for their potential implication in both the pathogenesis of degenerative neuromuscular diseases and as a possible therapeutic target. In this study, we screened the content of extracellular vesicles from animal models of muscle hypertrophy and muscle wasting associated with chronic disease and aging. Analysis of the transcriptome, protein cargo and microRNAs (miRNAs) allowed us to identify a hypertrophic miRNA signature amenable for targeting muscle wasting, consisting of miR-1 and miR-208a. We tested this signature among others in vitro on mesoangioblasts (MABs), vessel-associated adult stem cells, and we observed an increase in the efficiency of myogenic differentiation. Furthermore, injections of miRNA-treated MABs in aged mice resulted in an improvement in skeletal muscle features, such as muscle weight, strength and cross-sectional area compared to controls. Overall, we provide evidence that the extracellular vesicle-derived miRNA signature we identified enhances the myogenic potential of myogenic stem cells.
2022-11-09 | PXD035446 | Pride
Project description:Muscle function relies on the precise architecture of dynamic contractile elements, which must be fine-tuned to maintain motility throughout life. Muscle is also highly plastic, and remodeled in response to stress, growth, neural and metabolic inputs. The evolutionarily conserved muscle microRNA, mir1, regulates distinct aspects of muscle biology during development, but whether it plays a role during ageing is unknown. Here we investigated the role of C. elegans mir-1 in muscle function in response to proteostatic stress during adulthood. mir-1 deletion results in improved mid-life muscle motility, pharyngeal pumping, and organismal longevity under conditions of polyglutamine repeat proteotoxic challenge. We identified multiple vacuolar ATPase subunits as subject to mir-1 control, and the regulatory subunit vha-13/ATP6VIA as a direct target downregulated via its 3’UTR to mediate mir-1 physiology. mir-1 further regulates nuclear localization of lysosomal biogenesis factor HLH-30/TFEB and lysosomal acidification. Our studies reveal that mir-1 coordinately regulates lysosomal v-ATPase and biogenesis to impact muscle function and health during ageing.
2021-07-14 | PXD023544 | Pride
Project description:Healthy skeletal muscle can regenerate after ischaemic, mechanical, or toxin-induced injury, but ageing impairs that regeneration potential. This has been largely attributed to dysfunctional satellite cells and reduced myogenic capacity. Understanding which signalling pathways are associated with reduced myogenesis and impaired muscle regeneration can provide valuable information about the mechanisms driving muscle ageing and prompt the development of new therapies. To investigate this, we developed a high-throughput in vitro model to assess muscle regeneration in chemically injured C2C12 and human myotube-derived young and aged myoblast cultures. We observed a reduced regeneration capacity of aged cells, as indicated by an attenuated recovery towards preinjury myotube size and myogenic fusion index at the end of the regeneration period, in comparison with younger muscle cells that were fully recovered. RNA-sequencing data showed significant enrichment of KEGG signalling pathways, PI3K-Akt, and downregulation of GO processes associated with muscle development, differentiation, and contraction in aged but not in young muscle cells. Data presented here suggests that repair in response to in vitro injury is impaired in aged vs. young muscle cells. Our study establishes a framework that enables further understanding of the factors underlying impaired muscle regeneration in older age.
2023-07-05 | E-MTAB-12248 | biostudies-arrayexpress
Project description:Direct lineage reprogramming provides a unique system to study cell fate transitions and unearth molecular mechanisms that safeguard cellular identity. We previously reported on direct conversion of mouse fibroblasts into induced myogenic progenitor cells (iMPCs) by transient MyoD overexpression in concert with small molecules treatment. Here we employed integrative multi-omic approaches to delineate the molecular landscape of fibroblast reprogramming into iMPCs in comparison to transdifferentiation into myogenic cells solely by MyoD overexpression. Utilizing bulk RNA-sequencing and mass spectrometry, we uncovered molecular regulators and pathways that endow a myogenic stem cell identity on fibroblasts only in the presence of small molecule treatment. In addition, we demonstrate that Pax7+ cells in iMPCs share molecular attributes with myoblasts, however in addition express unique genes, proteins and pathways that are indicative of a more activated satellite cell-like state in vitro. Collectively, this study charts a molecular blueprint for reprogramming fibroblasts into muscle stem and progenitor cells and further establishes the fidelity of stable iMPC cultures in capturing skeletal muscle regeneration in vitro for disease modeling and basic research applications.
2022-05-19 | PXD029379 | Pride
Project description:Satellite cells (SCs), the skeletal muscle stem cells, display functional heterogeneity linked to their regenerative potential. Dramatic changes in their behaviour are also associated to muscle wasting diseases. Therefore, understanding the mechanisms controlling satellite cell heterogeneous behaviour during muscle regeneration and diseases has become increasingly important for regenerative medicine. Here, we show that miR-106bis expressed in Myf5- quiescent SCs and downregulated during SC activation and muscle regeneration. In vitro and in vivo studies to show that miR106b inhibition enhances the regenerative capability of murine and human SCs by increasing myogenic precursors. miR106b is increased in dystrophic mice and intramuscular injection of antimiR enhances muscle regeneration accompanied by significant functional recovery. miR-106b is also elevated in human dystrophic SCs and its inhibition improves intrinsic proliferative defects, increasing their myogenic differentiation potential. Therefore, this study identifies miR-106b as compelling candidate to consider for potential clinical studies.
2022-07-01 | GSE134111 | GEO
Project description:Skeletal muscle growth and regeneration rely on myogenic progenitor and satellite cells, the stem cells of postnatal muscle. Elimination of Notch signals during mouse development results in premature differentiation of myogenic progenitors and formation of very small muscle groups. Here we show that this drastic effect is rescued by mutation of the muscle differentiation factor MyoD. However, rescued myogenic progenitors do not assume a satellite cell position and contribute poorly to myofiber growth. The disrupted homing is due to a deficit in basal lamina assembly around emerging satellite cells and to their impaired adhesion to myofibers. On a molecular level, emerging satellite deregulate the expression of basal lamina components and adhesion molecules like integrin a7, collagen XVIIIa1, Megf10 and Mcam. We conclude that Notch signals control homing of satellite cells, stimulating them to contribute to their own microenvironment and to adhere to myofibers. Gene expression analysis using total RNA from FACS-isolated Vcam-1+/CD31-/CD45-/Sca1- embryonic muscle progenitor cells from E17.5 back muscle tissue of MyoD-/-, Pax3cre/+;Rbpjflox/flox;MyoD-/- and Pax3cre/+;DnMamlflox/flox;MyoD-/- mice.
2012-12-31 | E-GEOD-39379 | biostudies-arrayexpress
Project description:ObjectiveSkeletal muscle regeneration is markedly impaired during aging. How adult muscle stem cells contribute to this decrease in regenerative capacity is incompletely understood. We investigated mechanisms of age-related changes in myogenic progenitor cells using the tissue-specific microRNA 501.MethodsYoung and old C57Bl/6 mice were used (3 months or 24 months of age, respectively) with or without global or tissue-specific genetic deletion of miR-501. Muscle regeneration was induced using intramuscular cardiotoxin injection or treadmill exercise and analysed using single cell and bulk RNA sequencing, qRT-PCR and immunofluorescence. Muscle fiber damage was assessed with Evan`s blue dye (EBD). In vitro analysis was performed in primary muscle cells obtained from mice and humans.ResultsSingle cell sequencing revealed myogenic progenitor cells in miR-501 knockout mice at day 6 after muscle injury that are characterized by high levels of myogenin and CD74. In control mice these cells were less in number and already downregulated after day 3 of muscle injury. Muscle from knockout mice had reduced myofiber size and reduced myofiber resilience to injury and exercise. miR-501 elicits this effect by regulating sarcomeric gene expression through its target gene estrogen-related receptor gamma (Esrrg). Importantly, in aged skeletal muscle where miR-501 was significantly downregulated and its target Esrrg significantly upregulated, the number of myog+/CD74+ cells during regeneration was upregulated to similar levels as observed in 501 knockout mice. Moreover, myog+/CD74+-aged skeletal muscle exhibited a similar decrease in the size of newly formed myofibers and increased number of necrotic myofibers after injury as observed in mice lacking miR-501.ConclusionsmiR-501 and Esrrg are regulated in muscle with decreased regenerative capacity and loss of miR-501 is permissive to the appearance of CD74+ myogenic progenitors. Our data uncover a novel link between the metabolic transcription factor Esrrg and sarcomere formation and demonstrate that stem cell heterogeneity in skeletal muscle during aging is under miRNA control. Targeting Esrrg or myog+/CD74+ progenitor cells might improve fiber size and myofiber resilience to exercise in aged skeletal muscle.
| S-EPMC10033748 | biostudies-literature
Project description:Proctor2017 - Identifying microRNA for muscle
regeneration during ageing (Mirs_in_muscle)
This model is described in the article:
Using computer simulation
models to investigate the most promising microRNAs to improve
muscle regeneration during ageing
Carole J. Proctor & Katarzyna
Goljanek-Whysall
Nature Scientific Reports
Abstract:
MicroRNAs (miRNAs) regulate gene expression through
interactions with target sites within mRNAs, leading to
enhanced degradation of the mRNA or inhibition of translation.
Skeletal muscle expresses many different miRNAs with important
roles in adulthood myogenesis (regeneration) and myofibre
hypertrophy and atrophy, processes associated with muscle
ageing. However, the large number of miRNAs and their targets
mean that a complex network of pathways exists, making it
difficult to predict the effect of selected miRNAs on
age-related muscle wasting. Computational modelling has the
potential to aid this process as it is possible to combine
models of individual miRNA:target interactions to form an
integrated network. As yet, no models of these interactions in
muscle exist. We created the first model of miRNA:target
interactions in myogenesis based on experimental evidence of
individual miRNAs which were next validated and used to make
testable predictions. Our model confirms that miRNAs regulate
key interactions during myogenesis and can act by promoting the
switch between quiescent/proliferating/differentiating
myoblasts and by maintaining the differentiation process. We
propose that a threshold level of miR-1 acts in the initial
switch to differentiation, with miR-181 keeping the switch on
and miR-378 maintaining the differentiation and miR-143
inhibiting myogenesis.
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Chelliah V et al. BioModels: ten-year
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2017-09-26 | MODEL1704110004 | BioModels