Similar Datasets
Project description:Muscle stem cells, also known as satellite cells, are largely non-proliferative in uninjured skeletal muscle but transition at sites of injury into rapidly dividing progenitors that mediate muscle repair. As early events in satellite cell activation are rate-limiting for recovery from muscle damage, there is substantial interest in discovering their molecular driver(s). Using a comparative transcriptomic approach, we identified a prominent Fos signature in recently activated muscle satellite cells, which was rapidly and transiently induced by muscle damage. Functional interrogation using complementary genetic mouse models revealed that FOS is required for efficiently initiating key stem cell functions, including cell cycle entry, stem/progenitor cell expansion, and regeneration of muscle after injury. Transcriptional profiling further revealed that FOS activates critical gene circuits that stimulate cell migration, proliferation, and differentiation while simultaneously repressing quiescence-promoting gene signatures. Pharmacological and genetic disruption of one of these FOS-activated target genes, mono-ADP Ribosyl-Transferase 1 (Art1), in freshly isolated satellite cells substantially diminished cell cycle entry and expansion of the pool of regenerative stem cells. Together, these data implicate FOS as a crucial inducer of early-acting, pro-regenerative gene targets and highlight new transcriptional and post-translational modification events necessary for optimal injury-activated muscle stem cell regenerative responses.
2021-01-27 | GSE119695 | GEO
Project description:Muscle stem cells, also known as satellite cells, are largely non-proliferative in uninjured skeletal muscle but transition at sites of injury into rapidly dividing progenitors that mediate muscle repair. As early events in satellite cell activation are rate-limiting for recovery from muscle damage, there is substantial interest in discovering their molecular driver(s). Using a comparative transcriptomic approach, we identified a prominent Fos signature in recently activated muscle satellite cells, which was rapidly and transiently induced by muscle damage. Functional interrogation using complementary genetic mouse models revealed that FOS is required for efficiently initiating key stem cell functions, including cell cycle entry, stem/progenitor cell expansion, and regeneration of muscle after injury. Transcriptional profiling further revealed that FOS activates critical gene circuits that stimulate cell migration, proliferation, and differentiation while simultaneously repressing quiescence-promoting gene signatures. Pharmacological and genetic disruption of one of these FOS-activated target genes, mono-ADP Ribosyl-Transferase 1 (Art1), in freshly isolated satellite cells substantially diminished cell cycle entry and expansion of the pool of regenerative stem cells. Together, these data implicate FOS as a crucial inducer of early-acting, pro-regenerative gene targets and highlight new transcriptional and post-translational modification events necessary for optimal injury-activated muscle stem cell regenerative responses.
2021-01-27 | GSE119895 | GEO
Project description:Fos licenses early events in stem cell activation promoting skeletal muscle regeneration
| PRJNA490635 | ENA
Project description:Fos licenses early events in stem cell activation promoting skeletal muscle regeneration [array]
| PRJNA490031 | ENA
Project description:Fos licenses early events in stem cell activation promoting skeletal muscle regeneration [RNA-seq]
| PRJNA490637 | ENA
Project description:Regeneration of muscle fibers that are lost during pathological muscle degeneration or after injuries is sustained by the production of new myofibers. An important cell type involved in muscle regeneration is the satellite cell. Necdin is a protein expressed in satellite cell-derived myogenic precursors during perinatal growth. However, its function in myogenesis is not known. We compare transgenic mice that overexpress necdin in skeletal muscle with both wild-type and necdin null mice. After muscle injury the necdin null mice show a considerable defect in muscle healing, whereas mice that overexpress necdin show a substantial increase in myofiber regeneration. We also find that in muscle, necdin increases myogenin expression, accelerates differentiation, and counteracts myoblast apoptosis. Collectively, these data clarify the function and mechanism of necdin in skeletal muscle and show the importance of necdin in muscle regeneration.
| S-EPMC2064766 | biostudies-literature
Project description:Skeletal muscle comprises 30-40% of the weight of a healthy human body and is required for voluntary movements in humans. Mature skeletal muscle is formed by multinuclear cells, which are called myofibers. Formation of myofibers depends on the proliferation, differentiation, and fusion of muscle progenitor cells during development and after injury. Muscle progenitor cells are derived from muscle satellite (stem) cells (MuSCs), which reside on the surface of the myofiber but beneath the basement membrane. MuSCs play a central role in postnatal maintenance, growth, repair, and regeneration of skeletal muscle. In sedentary adult muscle, MuSCs are mitotically quiescent, but are promptly activated in response to muscle injury. Physiological and chronological aging induces MuSC aging, leading to an impaired regenerative capability. Importantly, in pathological situations, repetitive muscle injury induces early impairment of MuSCs due to stem cell aging and leads to early impairment of regeneration ability. In this review, we discuss (1) the role of MuSCs in muscle regeneration, (2) stem cell aging under physiological and pathological conditions, and (3) prospects related to clinical applications of controlling MuSCs.
| S-EPMC7084237 | biostudies-literature
Project description:Pathological conditions affecting skeletal muscle function may lead to irreversible volumetric muscle loss (VML). Therapeutic approaches involving acellular matrices represent an emerging and promising strategy to promote regeneration of skeletal muscle following injury. Here we investigated the ability of three different decellularised skeletal muscle scaffolds to support muscle regeneration in a xenogeneic immune-competent model of VML, in which the EDL muscle was surgically resected. All implanted acellular matrices, used to replace the resected muscles, were able to generate functional artificial muscles by promoting host myogenic cell migration and differentiation, as well as nervous fibres, vascular networks, and satellite cell (SC) homing. However, acellular tissue mainly composed of extracellular matrix (ECM) allowed better myofibre three-dimensional (3D) organization and the restoration of SC pool, when compared to scaffolds which also preserved muscular cytoskeletal structures. Finally, we showed that fibroblasts are indispensable to promote efficient migration and myogenesis by muscle stem cells across the scaffolds in vitro. This data strongly support the use of xenogeneic acellular muscles as device to treat VML conditions in absence of donor cell implementation, as well as in vitro model for studying cell interplay during myogenesis.
| S-EPMC5976677 | biostudies-literature
Project description:The thymus is the central immune organ, but it is known to progressively degenerate with age. As thymus degeneration is paralleled by the wasting of aging skeletal muscle, we speculated that the thymus may play a role in muscle wasting. Here, using thymectomized mice, we show that the thymus is necessary for skeletal muscle regeneration, a process tightly associated with muscle aging. Compared to control mice, the thymectomized mice displayed comparable growth of muscle mass, but decreased muscle regeneration in response to injury, as evidenced by small and sparse regenerative myofibers along with inhibited expression of regeneration-associated genes myh3, myod, and myogenin. Using paired box 7 (Pax7)-immunofluorescence staining and 5-Bromo-2'-deoxyuridine-incorporation assay, we determined that the decreased regeneration capacity was caused by a limited satellite cell pool. Interestingly, the conditioned culture medium of isolated thymocytes had a potent capacity to directly stimulate satellite cell expansion in vitro. These expanded cells were enriched in subpopulations of quiescent satellite cells (Pax7highMyoDlowEdUpos) and activated satellite cells (Pax7highMyoDhighEdUpos), which were efficiently incorporated into the regenerative myofibers. We thus propose that the thymus plays an essential role in muscle regeneration by directly promoting satellite cell expansion and may function profoundly in the muscle aging process.
| S-EPMC8752954 | biostudies-literature
Project description:Idiopathic inflammatory myopathies cause progressive muscle weakness and degeneration. Since high-dose glucocorticoids might not lead to full recovery of muscle function, physical exercise is also an important intervention, but some exercises exacerbate chronic inflammation and muscle fibrosis. It is unknown how physical exercise can have both beneficial and detrimental effects in chronic myopathy. Here we show that senescence of fibro-adipogenic progenitors (FAPs) in response to exercise-induced muscle damage is needed to establish a state of regenerative inflammation that induces muscle regeneration. In chronic inflammatory myopathy model mice, exercise does not promote FAP senescence or resistance against tumor necrosis factor-mediated apoptosis. Pro-senescent intervention combining exercise and pharmacological AMPK activation reverses FAP apoptosis resistance and improves muscle function and regeneration. Our results demonstrate that the absence of FAP senescence after exercise leads to muscle degeneration with FAP accumulation. FAP-targeted pro-senescent interventions with exercise and pharmacological AMPK activation may constitute a therapeutic strategy for chronic inflammatory myopathy.
| S-EPMC7021787 | biostudies-literature