Satellite Cells Choreograph an Immune Cell-Fibrogenic Cell Circuit During Mechanical Loading in Geriatric Skeletal Muscle
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PROVIDER: PRJNA1232112 | ENA |
REPOSITORIES: ENA
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Project description:Muscle stem cells, or satellite cells, decline in number with age and may become senescent. Whether and how satellite cells contribute to muscle adaptation in the oldest-old is unclear. Using short-term mechanical overload in geriatric satellite cell replete and depleted mice (28 months of age) combined with single cell RNA-sequencing, we show: 1) subsets of geriatric satellite cells show signs of senescence as well as normal fate progression during overload, 2) satellite cells express markers that may contribute to the regulation of innervation, 3) the presence of satellite cells during overload globally enhances intercellular communication and causes upregulation of the cell surface receptor gene Cd74 in immune cells, 4) Mif, the primary ligand for CD74, is produced by fibrogenic cells and is more pronounced in the absence of satellite cells - perhaps to help normalize dysregulated fibrotic signaling, and 5) satellite cells drive fate directive transcript splicing that promotes the canonical macrophage response to hypertrophic loading. Our findings expose the behavior of satellite cells in response to mechanical loading in the oldest-old and reveal a satellite cell-macrophage-fibrogenic cell circuit in geriatric muscle that may promote extracellular matrix remodeling
2025-08-28 | GSE291156 | GEO
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 with aging. Here we report that 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. 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 Young (2-3 months) and Geriatric (28-32 months) 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-53724 | biostudies-arrayexpress
Project description:A variety of epigenetic alterations impairs functions of cells and tissues during aging, but it is not known if epigenetic alterations are associated with aging muscle. Here, we examined the changes of a panel of histone marks and found H3K27ac (an active enhancer mark) is markedly increased during aging in human skeletal muscle tissues. Our integrated analysis showed that enhancer activation during muscle aging is associated with the up-regulation of extracelluar matrix (ECM) genes, which may result in stiffness of the niche environment of satellite cells (SCs). An age-related fibrogenic conversion of geriatric SCs was observed through differential gene expression analysis. In mice, treatment of aging muscles with JQ1, an inhibitor of enhancer activation reverted the ECM up-regulation and fibrogenic conversion of SCs, suggesting that ECM increase in aging muscle is indeed a result of enhancer activation. The study here not only uncovered a novel aspect of muscle aging that is associated with enhancer remodeling but also highlighted JQ1 as a potential treatment approach for restoring SC function in aging muscle.
2019-08-15 | GSE122867 | GEO
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 with aging and in progeric conditions. Here we report that 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. We analyzed the global changes in gene expression occurring within muscle stem cells (satellite cells) in homeostatic conditions during physiological aging and progeria. Pure satellite cell populations from dissociated skeletal muscle from Young (2-3 months), Old (22-24 months), Geriatric (28-30 months), SAMR1 and SAMP8 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-53725 | 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 with aging. Here we report that 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.
2013-12-31 | GSE53724 | GEO
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: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.
2013-12-31 | GSE53727 | GEO
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 with aging and in progeric conditions. Here we report that 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.
2013-12-31 | GSE53725 | GEO
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 with aging and in progeric conditions. Here we show that 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.
2013-12-31 | GSE53728 | GEO
Project description:Skeletal muscle is a plastic tissue, adapting to different stimuli. Mechanical overload causes muscle hypertrophy and substantial changes in gene expression. We perform a time course analysis following synergistic ablation surgery to induce compensatory hypertrophy in the plantaris muscle in satellite cell depleted mice and wild-type mice. Microarray was used to determine the different expressed genes in skeletal muscle with or without satellite cell following mechanical overload.
2021-07-12 | GSE153542 | GEO