| First Author | Tatsumi R | Year | 2017 |
| Journal | Stem Cells | Volume | 35 |
| Issue | 7 | Pages | 1815-1834 |
| PubMed ID | 28480592 | Mgi Jnum | J:250204 |
| Mgi Id | MGI:6093750 | Doi | 10.1002/stem.2639 |
| Citation | Tatsumi R, et al. (2017) Slow-Myofiber Commitment by Semaphorin 3A Secreted from Myogenic Stem Cells. Stem Cells 35(7):1815-1834 |
| abstractText | Recently, we found that resident myogenic stem satellite cells upregulate a multi-functional secreted protein, semaphorin 3A (Sema3A), exclusively at the early-differentiation phase in response to muscle injury; however, its physiological significance is still unknown. Here we show that Sema3A impacts slow-twitch fiber generation through a signaling pathway, cell-membrane receptor (neuropilin2-plexinA3) --> myogenin-myocyte enhancer factor 2D --> slow myosin heavy chain. This novel axis was found by small interfering RNA-transfection experiments in myoblast cultures, which also revealed an additional element that Sema3A-neuropilin1/plexinA1, A2 may enhance slow-fiber formation by activating signals that inhibit fast-myosin expression. Importantly, satellite cell-specific Sema3A conditional-knockout adult mice (Pax7CreER(T2) -Sema3A(fl) degrees (x) activated by tamoxifen-i.p. injection) provided direct in vivo evidence for the Sema3A-driven program, by showing that slow-fiber generation and muscle endurance were diminished after repair from cardiotoxin-injury of gastrocnemius muscle. Overall, the findings highlight an active role for satellite cell-secreted Sema3A ligand as a key "commitment factor" for the slow-fiber population during muscle regeneration. Results extend our understanding of the myogenic stem-cell strategy that regulates fiber-type differentiation and is responsible for skeletal muscle contractility, energy metabolism, fatigue resistance, and its susceptibility to aging and disease. Stem Cells 2017;35:1815-1834. |
