![]() Geriatric muscle stem cells switch reversible quiescence into senescence. ![]() Autophagy maintains stemness by preventing senescence. Transcriptional profiling of quiescent muscle stem cells in vivo. Expression of CD34 and Myf5 defines the majority of quiescent adult skeletal muscle satellite cells. Concise review: evidence for CD34 as a common marker for diverse progenitors. ImaGEO: integrative gene expression meta-analysis from GEO database. Single-cell analysis of the muscle stem cell hierarchy identifies heterotypic communication signals involved in skeletal muscle regeneration. PAX3 confers functional heterogeneity in skeletal muscle stem cell responses to environmental stress. Lineage tracing reveals a subset of reserve muscle stem cells capable of clonal expansion under stress. A subpopulation of adult skeletal muscle stem cells retains all template DNA strands after cell division. Rocheteau, P., Gayraud-Morel, B., Siegl-Cachedenier, I., Blasco, M. Asymmetric self-renewal and commitment of satellite stem cells in muscle. High-dimensional single-cell cartography reveals novel skeletal muscle-resident cell populations. Single cell analysis of adult mouse skeletal muscle stem cells in homeostatic and regenerative conditions. The aged niche disrupts muscle stem cell quiescence. Orienting muscle stem cells for regeneration in homeostasis, aging, and disease. Tissue-specific stem cells: lessons from the skeletal muscle satellite cell. Muscle stem cell aging: regulation and rejuvenation. Sousa-Victor, P., Garcia-Prat, L., Serrano, A. These findings reveal transcriptional determinants of stem-cell heterogeneity that resist ageing more than previously anticipated and are only lost in extreme old age, with implications for the repair of geriatric muscle. Interventions to neutralize Akt and promote FoxO activity drive a primed-to-genuine state conversion, whereas FoxO inactivation deteriorates the genuine state at a young age, causing regenerative failure of muscle, as occurs in geriatric mice. Niche-derived IGF1-dependent Akt activation debilitates the genuine stem-cell state by imposing primed-state features via FoxO inhibition. The genuine-quiescent state is unexpectedly preserved into later life, succumbing only in extreme old age due to the acquisition of primed-state traits. Here, in homeostatic skeletal muscle, we identify two quiescent stem-cell states distinguished by relative CD34 expression: CD34 High, with stemness properties (genuine state), and CD34 Low, committed to myogenic differentiation (primed state). Tissue regeneration declines with ageing but little is known about whether this arises from changes in stem-cell heterogeneity. Nature Cell Biology volume 22, pages 1307–1318 ( 2020) Cite this article FoxO maintains a genuine muscle stem-cell quiescent state until geriatric age
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