| First Author | Zismanov V | Year | 2016 |
| Journal | Cell Stem Cell | Volume | 18 |
| Issue | 1 | Pages | 79-90 |
| PubMed ID | 26549106 | Mgi Jnum | J:315396 |
| Mgi Id | MGI:6830334 | Doi | 10.1016/j.stem.2015.09.020 |
| Citation | Zismanov V, et al. (2016) Phosphorylation of eIF2alpha Is a Translational Control Mechanism Regulating Muscle Stem Cell Quiescence and Self-Renewal. Cell Stem Cell 18(1):79-90 |
| abstractText | Regeneration of adult tissues depends on somatic stem cells that remain quiescent yet are primed to enter a differentiation program. The molecular pathways that prevent activation of these cells are not well understood. Using mouse skeletal muscle stem cells as a model, we show that a general repression of translation, mediated by the phosphorylation of translation initiation factor eIF2alpha at serine 51 (P-eIF2alpha), is required to maintain the quiescent state. Skeletal muscle stem cells unable to phosphorylate eIF2alpha exit quiescence, activate the myogenic program, and differentiate, but do not self-renew. P-eIF2alpha ensures in part the robust translational silencing of accumulating mRNAs that is needed to prevent the activation of muscle stem cells. Additionally, P-eIF2alpha-dependent translation of mRNAs regulated by upstream open reading frames (uORFs) contributes to the molecular signature of stemness. Pharmacological inhibition of eIF2alpha dephosphorylation enhances skeletal muscle stem cell self-renewal and regenerative capacity. |
