Academic Journal
FoxO maintains a genuine muscle stem-cell quiescent state until geriatric age
| العنوان: | FoxO maintains a genuine muscle stem-cell quiescent state until geriatric age |
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| المؤلفون: | Garcia-Prat L., Perdiguero E., Alonso-Martin S., Dell'Orso S., Ravichandran S., Brooks S. R., Juan A. H., Campanario S., Jiang K., Hong X., Ortet L., Ruiz-Bonilla V., Flandez M., Moiseeva V., Rebollo E., Jardi M., Sun H. -W., MUSARO' A., Sandri M., Sol A., Sartorelli V., Munoz-Canoves P. |
| المساهمون: | Garcia-Prat, L., Perdiguero, E., Alonso-Martin, S., Dell'Orso, S., Ravichandran, S., Brooks, S. R., Juan, A. H., Campanario, S., Jiang, K., Hong, X., Ortet, L., Ruiz-Bonilla, V., Flandez, M., Moiseeva, V., Rebollo, E., Jardi, M., Sun, H. -W., Musaro', A., Sandri, M., Sol, A., Sartorelli, V., Munoz-Canoves, P. |
| بيانات النشر: | Nature Research Heidelberg |
| سنة النشر: | 2020 |
| المجموعة: | Sapienza Università di Roma: CINECA IRIS |
| مصطلحات موضوعية: | aging, satellite cell, foxO, stem-cell |
| الوصف: | 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: CD34High, with stemness properties (genuine state), and CD34Low, 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/33106654; info:eu-repo/semantics/altIdentifier/wos/WOS:000584081400002; volume:22; issue:11; firstpage:1307; lastpage:1318; numberofpages:12; journal:NATURE CELL BIOLOGY; http://hdl.handle.net/11573/1469084; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85094150502 |
| DOI: | 10.1038/s41556-020-00593-7 |
| الاتاحة: | http://hdl.handle.net/11573/1469084 https://doi.org/10.1038/s41556-020-00593-7 |
| Rights: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.64E1750D |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41556-020-00593-7 |
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