| First Author | Brien P | Year | 2013 |
| Journal | Stem Cells | Volume | 31 |
| Issue | 8 | Pages | 1597-610 |
| PubMed ID | 23592450 | Mgi Jnum | J:202729 |
| Mgi Id | MGI:5521275 | Doi | 10.1002/stem.1399 |
| Citation | Brien P, et al. (2013) p38alpha MAPK regulates adult muscle stem cell fate by restricting progenitor proliferation during postnatal growth and repair. Stem Cells 31(8):1597-610 |
| abstractText | Stem cell function is essential for the maintenance of adult tissue homeostasis. Controlling the balance between self-renewal and differentiation is crucial to maintain a receptive satellite cell pool capable of responding to growth and regeneration cues. The mitogen-activated protein kinase p38alpha has been implicated in the regulation of these processes but its influence in adult muscle remains unknown. Using conditional satellite cell p38alpha knockout mice we have demonstrated that p38alpha restricts excess proliferation in the postnatal growth phase while promoting timely myoblast differentiation. Differentiation was still able to occur in the p38alpha-null satellite cells, however, but was delayed. An absence of p38alpha resulted in a postnatal growth defect along with the persistence of an increased reservoir of satellite cells into adulthood. This population was still capable of responding to cardiotoxin-induced injury, resulting in complete, albeit delayed, regeneration, with further enhancement of the satellite cell population. Increased p38gamma phosphorylation accompanied the absence of p38alpha, and inhibition of p38gamma ex vivo substantially decreased the myogenic defect. We have used genome-wide transcriptome analysis to characterize the changes in expression that occur between resting and regenerating muscle, and the influence p38alpha has on these expression profiles. This study provides novel evidence for the fundamental role of p38alpha in adult muscle homeostasis in vivo. |
