Waking up muscle stem cells:
            <scp>PI</scp>
            3K signalling is ringing

Relaix, Frédéric; Machado, Léo

doi:10.15252/embj.201899297

Cited by 4 publications

(5 citation statements)

References 12 publications

(31 reference statements)

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“…Quiescent satellite cells in G 0 display a detectable low level of energy metabolism and predominantly derive their energy needs from glycolysis, unlike most G 1 -arrested cells that rely on oxidative phosphorylation [98][99][100]. Despite a preference for glycolysis in quiescent satellite cells, which does not rely on mitochondrial function [101], the ability to remove damaged mitochondria remains integral to maintaining cell viability.…”

Section: Quiescence Is a Double-edged Swordmentioning

confidence: 99%

Satellite cells in ageing: use it or lose it

2020

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Individuals that maintain healthy skeletal tissue tend to live healthier, happier lives as proper muscle function enables maintenance of independence and actuation of autonomy. The onset of skeletal muscle decline begins around the age of 30, and muscle atrophy is associated with a number of serious morbidities and mortalities. Satellite cells are responsible for regeneration of skeletal muscle and enter a reversible non-dividing state of quiescence under homeostatic conditions. In response to injury, satellite cells are able to activate and re-enter the cell cycle, creating new cells to repair and create nascent muscle fibres while preserving a small population that can return to quiescence for future regenerative demands. However, in aged muscle, satellite cells that experience prolonged quiescence will undergo programmed cellular senescence, an irreversible non-dividing state that handicaps the regenerative capabilities of muscle. This review examines how periodic activation and cycling of satellite cells through exercise can mitigate senescence acquisition and myogenic decline.

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Section: Quiescence Is a Double-edged Swordmentioning

confidence: 99%

Satellite cells in ageing: use it or lose it

2020

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“…Mouse muscle stem cells, called satellite cells because of their location on the periphery of the muscle, are mostly quiescent yet also rely heavily on glycolysis and have few mitochondria . Mouse muscle stem cells, like stem cells from other tissues, are reported to have high levels of glycolytic activity . Upon differentiation, mitochondrial density increases dramatically and newly formed mouse muscle cells rely on oxidative phosphorylation to provide energy for contraction .…”

Section: Adult Stem Cells Are Quiescent and Highly Glycolyticmentioning

confidence: 99%

The paradox of metabolism in quiescent stem cells

Coller

2019

FEBS Letters

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The shift between a proliferating and a nonproliferating state is associated with significant changes in metabolic needs. Proliferating cells tend to have higher metabolic rates, and their metabolic profiles facilitate biosynthesis, as compared to those of nondividing cells of the same sort. Recent studies have elucidated specific molecules that control metabolic changes while cells shift between proliferation and quiescence. Embryonic stem cells, which are rapidly proliferating, tend to have metabolic patterns that are similar to those of nonstem cells in a proliferative state. Moreover, although adult stem cells tend to be quiescent, their metabolic profiles have been reported in multiple organs to more closely resemble those of proliferating than those of nondividing cells in some respects. The findings raise questions about whether there are metabolic profiles that are required for stemness, and whether these profiles relate to the metabolic properties that may be required for quiescence. Here, we review the literature on how metabolism changes upon commitment to proliferation and compare the proliferating and nonproliferating metabolic states of differentiated cells and embryonic and adult stem cells.

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“…Consistent with the phenotype of GR MuSC-/mice, constitutive PI3K signalling results in precocious exit from quiescence and nuclear accretion via fusion to existing myofibers in the absence of injury (50,67,68). Conditional knockout of P110α in MuSCs prevents MuSCs from exiting quiescence following injury and impairs muscle regeneration (50,68). PI3K activity inhibits FOXO3A activity and stimulates mTORC, which has been implicated in the regulation of the Galert state (67).…”

Section: Discussionmentioning

confidence: 71%

“…Functionally, Pik3r1 encodes a negative regulator of PI3K, acting to block the enzymatic activity of the p110 subunit (66), which, in turn, has been shown to be both necessary and sufficient for quiescence exit in adult MuSC (50). Consistent with the phenotype of GR MuSC-/mice, constitutive PI3K signalling results in precocious exit from quiescence and nuclear accretion via fusion to existing myofibers in the absence of injury (50,67,68). Conditional knockout of P110α in MuSCs prevents MuSCs from exiting quiescence following injury and impairs muscle regeneration (50,68).…”

Section: Discussionmentioning

confidence: 87%

The glucocorticoid receptor is a critical regulator of muscle satellite cell quiescence

Rajgara,

AlSudais,

Saleh

et al. 2023

Preprint

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Glucocorticoids are powerful anti-inflammatory medications that are associated with muscle atrophy. The effect of glucocorticoids in myofibers is well-studied, yet the role of the glucocorticoid receptor (GR), the primary mediator of glucocorticoid transcriptional responses, and the impact of glucocorticoid signalling in muscle stem cells (MuSCs), the adult progenitors responsible for regeneration, remain unknown. We developed a conditional null mouse model to knock out glucocorticoid receptor (GR) expression in MuSCs (GRMuSC-/-) and established that while GR is dispensable for muscle regeneration, it is a critical regulator of MuSC homeostasis. Loss of GR significantly increased cycling MuSCs as compared to controls in injury-naïve mice and on single EDL myofiber cultures, and as such, loss of GR in MuSCs leads to precocious activation and subsequent proliferation as compared to controls. Bulk RNA-sequencing fromin situfixed MuSCs from injury-naïve GRMuSC-/-muscle identified a gene signature consistent with cells that have exited quiescence and undergone activation, with evidence of sexual dimorphism. Using ATAC-seq and footprinting we identify putative GR targets that promote quiescence. Thus, we advance the GR as a previously unrecognized crucial transcriptional regulator of gene expression in MuSCs whose activity is highest in quiescent cells and is essential to maintain that state.

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Waking up muscle stem cells: PI 3K signalling is ringing

Cited by 4 publications

References 12 publications

Satellite cells in ageing: use it or lose it

Satellite cells in ageing: use it or lose it

The paradox of metabolism in quiescent stem cells

The glucocorticoid receptor is a critical regulator of muscle satellite cell quiescence

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