Lgr5 Marks Adult Progenitor Cells Contributing to Skeletal Muscle Regeneration and Sarcoma Formation

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Lgr5 Marks Adult Progenitor Cells Contributing to Skeletal Muscle Regeneration and Sarcoma Formation
Title:
Lgr5 Marks Adult Progenitor Cells Contributing to Skeletal Muscle Regeneration and Sarcoma Formation
Other Titles:
Cell Reports
Keywords:
Publication Date:
22 December 2020
Citation:
Leung, C., Murad, K.B.A., Tan, A.L.T., Yada, S., Sagiraju, S., Bode, P.K., and Barker, N. (2020). Lgr5 Marks Adult Progenitor Cells Contributing to Skeletal Muscle Regeneration and Sarcoma Formation. Cell Rep. 33, 108535.
Abstract:
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/β-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 Lgr5-2ACreERT2R26tdTomatoLSL 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 Lgr52ACreERT2;KrasG12D;Trp53flox/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.
License type:
http://creativecommons.org/licenses/by/4.0/
Funding Info:
This research is supported by the National Research Foundation, Prime Minister’s Office, Singapore under its Investigatorship Program (award no. NRF-NRF12017-03 )
Description:
ISSN:
22111247
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