The regenerating skeletal muscle niche guides muscle stem cell self-renewal Journal Article uri icon



  • SummarySkeletal muscle stem cells (MuSCs) are essential for muscle regeneration and maintenance. While MuSCs typically are quiescent and reside in an asymmetric niche between the basal lamina and myofiber membrane: to repair or maintain muscle, MuSCs activate, proliferate and differentiate to repair injured tissue, and self-renew to replenish MuSCs. Little is known about the timing of MuSC self-renewal during muscle regeneration and the cellular processes that direct MuSC self-renewal fate decisions. Using DNA-based lineage tracing, we find that during muscle regeneration most MuSCs self-renew from 5-7 days post-injury, following fusion of myogenic cells to regenerate myofibers. Single cell sequencing of the myogenic cells in regenerating muscle reveals that non-cell autonomous signaling networks regulate MuSC self-renewal allowing identification of asymmetrically distributed proteins in self-renewing MuSCs. Cell transplantation experiments verified that the regenerating environment signals MuSC self-renewal. Our results define the critical window for MuSC self-renewal emphasizing the temporal contribution of the regenerative muscle environment on MuSC fate, establishing a new paradigm for restoring the MuSC pool during muscle regeneration.

publication date

  • May 13, 2019

has restriction

  • green

Date in CU Experts

  • January 31, 2023 9:27 AM

Full Author List

  • Cutler AA; Pawlikowski B; Wheeler JR; Betta ND; Elston T; O‚ÄôRourke R; Jones K; Olwin BB

author count

  • 8

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