Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2023.06.19.545587v1?rss=1

Authors: Ancel, S., Michaud, J., Sizzano, F., Tauzin, L., Oliveira, M., Migliavacca, E., Dammone, G., Karaz, S., Sanchez-Garcia, J. L., Metairon, S., Jacot, G., Bentzinger, F. C., Feige, J. N., Stuelsatz, P.

Abstract:
Increasing evidence suggests that muscle stem cells (MuSCs) are a heterogeneous population. In particular, a rare subset of Pax7 positive MuSCs that has never expressed the myogenic regulatory factor Myf5 has been shown to have superior self-renewal and engraftment characteristics when compared to lineage positive cells. However, their scarcity and the limited availability of protein markers make the characterization of this MuSC subpopulation challenging. Complementing lineage tracing approaches, we developed the StemRep in vivo model with reporter alleles allowing to monitor Pax7 and Myf5 protein levels based on equimolar amounts of dual nuclear fluorescence. Using transcriptomic profiling and ex vivo cellular assays, we demonstrate that levels of Pax7 and Myf5 protein delineate subpopulations of MuSCs with distinct molecular signatures and dynamics of activation, proliferation, and commitment. MuSCs expressing high levels of Pax7 protein (Pax7high) and low levels of Myf5 (Myf5Low) retain phenotypic features and molecular signatures of quiescence, and transiently remodel during regeneration. The Pax7 reporter tracks the decline of the MuSC pool during aging, while the Myf5 reporter enables live monitoring of the age-related loss of quiescence via skewing of the MuSC population towards Myf5High. Altogether, we characterize Pax7highMyf5Low MuSCs as an uncommitted subpopulation in deep quiescence and establish the StemRep line as a novel versatile tool for the physiological study of stem cell dynamics in skeletal muscle.

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