Muscle satellite cell specific proteasome deficient mice
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ABSTRACT:
PROVIDER: PRJNA471084 | ENA |
REPOSITORIES: ENA
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Project description:Adult muscle stem cells (satellite cells) are required for adult skeletal muscle regeneration. A proper balance between quiescence, proliferation, and differentiation is essential for the maintenance of the satellite cell pool and their regenerative function. Although the ubiquitin-proteasome is required for most protein degradation in mammalian cells, how its dysfunction affects tissue stem cells remains unclear. Here, we investigated the function of the proteasome in satellite cells using mice lacking the crucial proteasomal component, Rpt3. Ablation of Rpt3 in satellite cells decreased proteasome activity. Proteasome dysfunction in Rpt3-deficient satellite cells impaired their ability to proliferate, survive and differentiate, resulting in defective muscle regeneration. We found that inactivation of proteasomal activity induced proliferation defects and apoptosis in satellite cells. Mechanistically, insufficient proteasomal activity upregulated the p53 pathway, which caused cell-cycle arrest. Our findings delineate a critical function of the proteasome system in maintaining satellite cells in adult muscle.
2018-10-10 | GSE114354 | GEO
Project description:The ubiquitin-proteasome and autophagy-lysosome pathways are the two major routes for protein and organelle clearance. In skeletal muscle, both systems’ excessive activation induces severe muscle loss. Although altered proteasomal function has been observed in various myopathies, the specific role of proteasomal activity in skeletal muscle has not been determined by loss-of-function approaches. Here, we report that muscle-specific deletion of a crucial proteasomal gene, Rpt3, resulted in profound muscle atrophy and decrease in force. Rpt3 null muscles showed reduced proteasomal activity in early age, accumulation of basophilic structure, disorganization of sarcomere, and formation of vacuoles and concentric membranous structures in electronmicroscope. We also observed accumulation of ubiquitin, p62, LC3, TDP43, FUS and VCP proteins. Proteasomal activity is important to preserve muscle mass and to maintain myofiber integrity. Our results suggest that inhibition/alteration of proteasomal activity can contribute to myofiber degeneration and weakness in muscle disorders, such as inclusion body myositis, characterized by accumulation of abnormal inclusions. Tibialis anterior muscles from Rpt3 null and control mice. each 3 mice.
2014-09-30 | E-GEOD-34896 | biostudies-arrayexpress
Project description:The ubiquitin-proteasome and autophagy-lysosome pathways are the two major routes for protein and organelle clearance. In skeletal muscle, both systems’ excessive activation induces severe muscle loss. Although altered proteasomal function has been observed in various myopathies, the specific role of proteasomal activity in skeletal muscle has not been determined by loss-of-function approaches. Here, we report that muscle-specific deletion of a crucial proteasomal gene, Rpt3, resulted in profound muscle atrophy and decrease in force. Rpt3 null muscles showed reduced proteasomal activity in early age, accumulation of basophilic structure, disorganization of sarcomere, and formation of vacuoles and concentric membranous structures in electronmicroscope. We also observed accumulation of ubiquitin, p62, LC3, TDP43, FUS and VCP proteins. Proteasomal activity is important to preserve muscle mass and to maintain myofiber integrity. Our results suggest that inhibition/alteration of proteasomal activity can contribute to myofiber degeneration and weakness in muscle disorders, such as inclusion body myositis, characterized by accumulation of abnormal inclusions.
2014-09-30 | GSE34896 | GEO
Project description:Muscle satellite cells (MuSCs), skeletal muscle-resident stem cells, are crucial for regeneration of myofibers. Mechanical cues are thought to be important for activation and proliferation of muscle satellite cells, but the molecular entity that senses biophysical forces in MuSCs remains to be elucidated. In this study, we identified PIEZO1, a mechanosensitive ion channel that is activated by membrane tension, as a critical determinant for myofiber regeneration. We investigated gene profiles of Piezo1-deficient MuSCs to understand the role of PIEZO1 during myogenesis. Our results suggest that PIEZO1 governs the cytoskeletal reorganization to regulate cellular events in MuSCs (i.e., activation, cell-division, and proliferation) during skeletal muscle regeneration.
2022-11-18 | GSE217417 | GEO
Project description:RNA-seq was performed to investigate the role of Rrm2b in skeletal muscle. Type II skeletal muscle fibers were collected from wild-type (C57BL/6) mice and two Rrm2b knockout models, the skeletal muscle-specific knockout (Rrm2b F/F;HSA-Cre, smKO) and satellite cell-specific knockout (Rrm2b F/F;Pax7-CreERT2, scKO).
2022-07-25 | E-MTAB-11318 | biostudies-arrayexpress
Project description:(Abstract of publication submitted currently) To clarify molecular regulation of satellite cells, we performed genome-wide gene expression analysis of quiescent satellite cells isolated from mouse skeletal muscle by flow cytometry. We identified 53 novel quiescent satellite cell-specific genes whose expressions are sharply down-regulated upon activation. The gene list contains a number of cell surface molecules, transcriptional factors, and cytokines and other signal transduction molecules. We further confirmed that Odz4 and calcitonin receptor proteins were expressed by quiescent but not by activated satellite cells in vivo. Importantly, we found that Pax7+/calcitonin receptor+ satellite cells reappear in close association with regenerating myofibers 7 days after muscle damage, often outside the basal lamina. Moreover, an agonist of calcitonin receptor suppressed the activation of quiescent satellite cells on myofibers in in vitro culture, suggesting that calcitonin receptor signaling plays an important role in renewal and maintenance of satellite cells. Our results show the gene expression profile of quiescent satellite cells for the first time and reveal the temporal and spatial reappearance of a satellite cell pool. Experiment Overall Design: Satellite cells and non-satellite cells were examined. Totally three types of cells (groups), the satellite cells in quiescent and activated states and the non-satellite cells, were compared. Each has 4 replicates.
2008-06-12 | E-GEOD-3483 | biostudies-arrayexpress
Project description:Satellite cells are resident skeletal muscle stem cells responsible for muscle maintenance and repair. In resting muscle, satellite cells are maintained in a quiescent state. Satellite cell activation induces the myogenic commitment factor, MyoD, and cell cycle entry to facilitate transition to a population of proliferating myoblasts that eventually exit the cycle and regenerate muscle tissue. The molecular mechanism involved in the transition of a quiescent satellite cell to a transit-amplifying myoblast is poorly understood. We used microarrays to detail the global program of gene expression of in vivo satellite cell activation through muscle injury and identified RNA post-transcriptional regulation as a key component of satellite cell activation. Wild type or Sdc4-/- satellite cells were FACS isolated from resting muscle or from muscle 12h and 48h following barium chloride-induced muscle injury. 5000 cell equivalents of RNA was labeled and hybridized to MOE430v2 GeneChips (Affymetrix) and scanned as per manufacturers protocol. Probeset intensities were GCRMA normalized for further analysis including UPGMA hierarchical clustering, analysis of variance (ANOVA), and fold change.
2012-07-31 | E-GEOD-38870 | biostudies-arrayexpress
Project description:Regeneration of skeletal muscle depends on a population of adult stem cells (satellite cells) that remain quiescent throughout life. Satellite cell regenerative functions decline in geriatric satellite cells, compared to old cells are incapable of maintaining their normal quiescent state in muscle homeostatic conditions, and this irreversibly affects their intrinsic regenerative and self-renewal capacities. In geriatric mice, resting satellite cells lose reversible quiescence by switching to an irreversible pre-senescence state, caused by derepression of p16INK4a. Young Bmi1-deficient satellite cells shares similar features. We analyzed the global changes in gene expression occurring within muscle stem cells (satellite cells) in homeostatic conditions during physiological aging. Pure satellite cell populations from dissociated skeletal muscle from WT and Bmi1-deficient mice were isolated using a well-established flow cytometry protocol gating on integrin a7(+)/CD34(+) (positive selection) and Lin- (CD31, CD45, CD11b, Sca1) (negative selection).
2013-12-31 | E-GEOD-53727 | biostudies-arrayexpress
Project description:To identify the target genes of Dnmt1 in skeletal muscle satellite cells, we generated satellite cell specific Dnmt1 KO using Pax7-CreERT2 and Dnmt1 flox mice. After Tamoxifen (cKO) or vehicle (Control) treatment for 5 consecutive days, mice were euthanized and muscle satellite cells were collected by FACS sorting and total RNA were extracted.
2021-01-08 | GSE156978 | GEO
Project description:Skeletal muscle is the most common tissue in the body. Its continued maintenance and regeneration throughout life is essential to the function of the organism. Satellite cells are critical to regeneration of the skeletal muscle and strategies to improve function of satellite cells are of great importance. Muscle-resident Fibro-Adipogenic Precursors (FAPs) cells are a critical component of the satellite cell niche and help orchestrate efficient muscle regeneration and potentiate satellite cell differentiation via soluble or secreted factors. Populations with similar phenotype and function to muscle FAPs have been isolated from the skin and white adipose tissue. Interactions between tissue-specific FAP cells and resident stem cells in those tissues might be conserved. Therefore, defining specific factors that mediate the relationship between muscle FAPs and satellite cells would have implications for other organs.
2019-06-30 | GSE67117 | GEO