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Graded regulation of cellular quiescence depth between proliferation and senescence by a lysosomal dimmer switch

ABSTRACT: Graded regulation of cellular quiescence depth between proliferation and senescence by a lysosomal dimmer switch

PROVIDER: PRJNA510786 | ENA |

REPOSITORIES: ENA

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Graded regulation of cellular quiescence depth between proliferation and senescence by a lysosomal dimmer switch

Project description:The reactivation of quiescent cells to proliferate is fundamental to tissue repair and homeostasis in the body. Often referred to as the G0 state, quiescence is however not a uniform state but with graded depth. Shallow quiescent cells exhibit a higher tendency to revert to proliferation than deep quiescent cells, while deep quiescent cells are still fully reversible under physiological conditions, distinct from senescent cells. Cellular mechanisms underlying the control of quiescence depth and the connection between quiescence and senescence are poorly characterized, representing a missing link in our understanding of tissue homeostasis and regeneration. Here we measured transcriptome changes as rat embryonic fibroblasts moved from shallow to deep quiescence over time in the absence of growth signals. We found that lysosomal gene expression was significantly upregulated in deep quiescence, and partially compensated for gradually reduced autophagy flux. Reducing lysosomal function drove cells progressively deeper into quiescence and eventually into a senescence-like irreversibly arrested state; increasing lysosomal function, by lowering oxidative stress, progressively pushed cells into shallower quiescence. That is, lysosomal function modulates graded quiescence depth between proliferation and senescence as a dimmer switch. Lastly, we found that a gene expression signature developed by comparing deep and shallow quiescence in fibroblasts can correctly classify a wide array of senescent and aging cell types in vitro and in vivo, suggesting that while quiescence is generally considered to protect cells from irreversible arrest of senescence, quiescence deepening likely represents a common transition path from cell proliferation to senescence, related to aging.

2019-10-11 | GSE124109 | GEO

Graded regulation of cellular quiescence depth between proliferation and senescence by a lysosomal dimmer switch.

Project description: Not available

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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 4; Bmi1-deficient)

2013-12-31 | GSE53727 | GEO

Controlling Depth of Cellular Quiescence by an Rb-E2F Network Switch.

Project description: Not available

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Gene expression profiling: Quiescence vs. Senescence

Project description:Using cDNA arrays, we compared the reversible (quiescence) and irreversible (senescence) growth arrest conditions in osteosarcoma cell line, U2OS, which resulted in certain overlapping and unique gene expression signatures.

2017-10-01 | GSE94805 | GEO

Geriatric muscle stem cells switch reversible quiescence into senescence

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-12-31 | E-GEOD-53728 | biostudies-arrayexpress

Transcriptome-profiling (RNA-seq) and Ribosome-profiling (Ribo-seq) in proliferation, quiescence, senescence and transformed states.

Project description:We applied in parallel RNA-Seq and Ribosome-profiling analyses to immortalized human primary BJ fibroblast cells under the following conditions: normal proliferation, quiescence (induced by serum depletion), senescence (induced by activation of the oncogenic RASG12V gene, and examined at early (5 days; pre-senescent state) and late (14 days; fully senescent state) time points), and neoplastic transformation (induced by RASG12V in the background of stable p53 and p16INK4A knockdowns and SV40 small-T expression. RNA-seq, using Illumina HiSeq 2000, was applied to BJ cells under 5 conditions: proliferation, quiescence, pre-senescence, full-senescence, and transfomed. Ribosome profiling, using Illumina HiSeq 2000, was applied to BJ cells under 5 conditions: proliferation, quiescence, pre-senescence, full-senescence, and transfomed.

2013-03-24 | E-GEOD-42509 | biostudies-arrayexpress

Impact of graded calorie restriction on mouse liver protein expression

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2023-10-24 | PXD033436 | Pride

Geriatric muscle stem cells switch reversible quiescence into senescence

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

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