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

Tal Falick Michaeli, Ofra Sabag, Rimma Fok, Batia Azria, Jonathan Monin, Yuval Nevo, Yuval Gielchinsky, Benjamin P. Berman, Howard Cedar*, Yehudit Bergman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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

Original languageEnglish
Article numbere2212306119
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number52
StatePublished - 27 Dec 2022
Externally publishedYes


FundersFunder number
German-Israel Foundation1424
Israel Science Foundation-physician scientist3181/20
Israel Cancer Research Fund211410, 210910
Deutsches Krebsforschungszentrum
Rosetrees Trust
Ministry of Science, Technology and Space
United States-Israel Binational Science Foundation2100289
Israel Science Foundation1228/18, 419/10


    • development
    • epigenetics
    • priming


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