| First Author | García-Prat L | Year | 2020 |
| Journal | Nat Cell Biol | Volume | 22 |
| Issue | 11 | Pages | 1307-1318 |
| PubMed ID | 33106654 | Mgi Jnum | J:310142 |
| Mgi Id | MGI:6709607 | Doi | 10.1038/s41556-020-00593-7 |
| Citation | Garcia-Prat L, et al. (2020) FoxO maintains a genuine muscle stem-cell quiescent state until geriatric age. Nat Cell Biol 22(11):1307-1318 |
| abstractText | Tissue regeneration declines with ageing but little is known about whether this arises from changes in stem-cell heterogeneity. 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). The genuine-quiescent state is unexpectedly preserved into later life, succumbing only in extreme old age due to the acquisition of primed-state traits. Niche-derived IGF1-dependent Akt activation debilitates the genuine stem-cell state by imposing primed-state features via FoxO inhibition. 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. 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. |
