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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE155642 | GEO | 2020/10/29

REPOSITORIES: GEO

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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

FoxO maintains a genuine quiescent muscle stem-cell state until geriatric age

Project description:FoxO maintains a genuine quiescent muscle stem-cell state until geriatric age

| PRJNA661758 | ENA

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

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

| PRJNA661759 | ENA

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

Project description:FoxO maintains a genuine quiescent muscle stem-cell state until geriatric age (ATAC-seq)

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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 2; Old/Geriatric vs. Young and SAMR1 vs. SAMP8)

2013-12-31 | GSE53725 | GEO

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

2013-12-31 | GSE53728 | GEO

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 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.

2013-12-31 | GSE53727 | GEO

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