TY - JOUR PY - 2022// TI - Muscle injury causes long-term changes in stem-cell DNA methylation JO - Proceedings of the National Academy of Sciences of the United States of America A1 - Falick Michaeli, Tal A1 - Sabag, Ofra A1 - Fok, Rimma A1 - Azria, Batia A1 - Monin, Jonathan A1 - Nevo, Yuval A1 - Gielchinsky, Yuval A1 - Berman, Benjamin P. A1 - Cedar, Howard A1 - Bergman, Yehudit SP - e2212306119 EP - e2212306119 VL - 119 IS - 52 N2 - 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.

Language: en

LA - en SN - 0027-8424 UR - http://dx.doi.org/10.1073/pnas.2212306119 ID - ref1 ER -