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Geriatric muscle stem cells switch reversible quiescence into senescence

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE53728 | GEO | 2013/12/31

SECONDARY ACCESSION(S): PRJNA232724

REPOSITORIES: GEO

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Geriatric muscle stem cells switch reversible quiescence into senescence (Set 1; Geriatric vs. Young)

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

Geriatric muscle stem cells switch reversible quiescence into senescence (Set 1; Geriatric vs. Young)

2013-12-31 | GSE53724 | GEO

Geriatric muscle stem cells switch reversible quiescence into senescence (Set 4; Bmi1-deficient)

2013-12-31 | GSE53727 | GEO

Geriatric muscle stem cells switch reversible quiescence into senescence (Set 3; Adult vs. Young)

2013-12-31 | GSE53726 | GEO

Geriatric muscle stem cells switch reversible quiescence into senescence (Set 4; Bmi1-deficient)

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

Geriatric muscle stem cells switch reversible quiescence into senescence (Set 2; Old/Geriatric vs. Young and SAMR1 vs. SAMP8)

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

Geriatric muscle stem cells switch reversible quiescence into senescence (Set 2; Old/Geriatric vs. Young and SAMR1 vs. SAMP8)

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

Geriatric muscle stem cells switch reversible quiescence into senescence (Set 3; Adult vs. Young)

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. We report that geriatric satellite cells, compared to old and adult 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 Adult (6 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-53726 | biostudies-arrayexpress

Epigenetic determinants of muscle stem cell quiescence and chronological aging

Project description:Skeletal muscle is a post-mitotic tissue that exhibits an extremely low turnover in the absence of disease or injury. At the same time, muscle possesses remarkable regenerative capacity mediated by satellite cells (SCs) that reside in close association with individual myofibers, underneath the fiber’s basal lamina. Consistent with the low turnover of the muscle, SCs in adult animals are mitotically quiescent and therefore provide an excellent model to study stem cell quiescence. As an organism grows older, the resident stem cells are exposed to a deteriorating environment and experience chronological aging. In stem cells with high turnover, the effects of chronological aging are superimposed upon the effects of the replicative aging that results from DNA replication and cell division. On the contrary, SCs experience minimal replicative aging due to their low turnover. They are thus a good model to study the consequence of chronological aging of quiescent stem cells. We performed microarray analysis of quiescent and activated SCs from both young and aged mice to understand the global gene expression profile underlying stem cell properties such as quiecence and self-renewal, and to understand how the transcriptome of a quiescent stem cell pouplation changes with age. VCAM+/CD31-/CD45-/Sca1- quiescent satellite cells (QSCs) were isolated by FACS from hindlimb muscle of uninjured 2-3- or 22-24-month old mice. Activated satellite cells (ASCs) were isolated from hindlimb muscles of BaCl2-injured mice of the same age 36, 60 and 84 hours after injury using the same cell surface marker combination. YFP-expressing cells were isolated from 2-3-month old Pax7CreER/+; ROSA26eYFP/+ mice in which satellite cells are labeled geneticall by YFP expression. Total RNA was extracted from cells with the Trizol reagent according to manufacturer's instructions. RNA was then processed and assayed with Affymetrix Mouse Gene 1.0 ST arrays.

2013-05-23 | E-GEOD-47177 | biostudies-arrayexpress

FoxO maintains a genuine quiescent muscle stem-cell state until geriatric age (RNA-seq)

Project description:We identify two quiescent stem-cell states through relative CD34 expression: CD34High, with stemness properties (genuine state), and CD34Low, more committed to myogenic differentiation (primed state). The genuine-quiescent state is preserved into later life succumbing only in extreme old age due to acquisition of primed-state traits. We identified niche-derived IGF1-dependent Akt activation as detrimental to the genuine stem-cell state by imposing primed-state features via FoxO inhibition. Interventions to neutralize Akt and promote FoxO activity drive primed-to-genuine state conversion, while FoxO inactivation deteriorates the genuine state at young age, causing muscle regenerative failure, as in geriatric mice.

2020-10-29 | GSE157562 | GEO

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