Muscle injury causes long-term changes in stem-cell DNA methylation

• DOI: 10.1073/pnas.2212306119
• Publication Date: 2022-12-19T20:09:05Z
• Authors: Tal Falick Michaeli; Ofra Sabag; Rimma Fok; Batia Azria; Jonathan Monin; Yuval Nevo; Yuval Gielchinsky; Benjamin P. Berman; Howard Cedar; Yehudit Bergman
• Keywords: Stem Cells; Animals; Regeneration; Female; Cell Differentiation; Biological Sciences; DNA Methylation; Muscle, Skeletal; Muscle Development; Epigenesis, Genetic

Injury to muscle brings about the activation of stem cells, which then generate new myocytes replace damaged tissue. We demonstrate that this is accompanied by a dramatic change in stem-cell methylation pattern prepares them epigenetically for terminal myocyte differentiation. These de- and de novo events occur at regulatory elements associated with genes involved myogenesis are necessary regeneration. Local injury one elicits an almost identical epigenetic satellite cells from other muscles body, process mediated circulating factors. Furthermore, same state also generated (MuSCs) female animals following pregnancy, even absence any injury. Unlike activation-induced expression changes, transient, induced profile stably maintained resident MuSCs thus represents molecular memory previous physiological probably programmed provide mechanism long-term adaptation.