| First Author | Leung C | Year | 2020 |
| Journal | Cell Rep | Volume | 33 |
| Issue | 12 | Pages | 108535 |
| PubMed ID | 33357435 | Mgi Jnum | J:301685 |
| Mgi Id | MGI:6489182 | Doi | 10.1016/j.celrep.2020.108535 |
| Citation | Leung C, et al. (2020) Lgr5 Marks Adult Progenitor Cells Contributing to Skeletal Muscle Regeneration and Sarcoma Formation. Cell Rep 33(12):108535 |
| abstractText | Regeneration of adult skeletal muscle is driven largely by resident satellite cells, a stem cell population increasingly considered to display a high degree of molecular heterogeneity. In this study, we find that Lgr5, a receptor for Rspo and a potent mediator of Wnt/beta-catenin signaling, marks a subset of activated satellite cells that contribute to muscle regeneration. Lgr5 is found to be rapidly upregulated in purified myogenic progenitors following acute cardiotoxin-induced injury. In vivo lineage tracing using our Lgr5-2ACre(ERT2)R26tdTomato(LSL) reporter mouse model shows that Lgr5(+) cells can reconstitute damaged muscle fibers following muscle injury, as well as replenish the quiescent satellite cell pool. Moreover, conditional mutation in Lgr52ACre(ERT2);Kras(G12D);Trp53(flox/flox) mice drives undifferentiated pleomorphic sarcoma formation in adult mice, thereby substantiating Lgr5(+) cells as a cell of origin of sarcomas. Our findings provide the groundwork for developing Rspo/Wnt-signaling-based therapeutics to potentially enhance regenerative outcomes of skeletal muscles in degenerative muscle diseases. |
