PLX162356

GSE157562: FoxO maintains a genuine quiescent muscle stem-cell state until geriatric age (RNA-seq)

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

We identify two quiescent stem-cell states through relative CD34 expression: CD34High, with stemness properties (genuine state), and CD34Low, more committed to myogenic differentiation (primed state). The genuine-quiescent state is preserved into later life succumbing only in extreme old age due to acquisition of primed-state traits. We identified niche-derived IGF1-dependent Akt activation as detrimental to the genuine stem-cell state by imposing primed-state features via FoxO inhibition. Interventions to neutralize Akt and promote FoxO activity drive primed-to-genuine state conversion, while FoxO inactivation deteriorates the genuine state at young age, causing muscle regenerative failure, as in geriatric mice. SOURCE: Stephen,R,Brooks (stephen.brooks@nih.gov) - NIAMS/NIH