Satellite cells represent the main myogenic population accounting for skeletal muscle homeostasis and regeneration. While our knowledge of the signaling pathways controlling satellite cell regenerative capability is increasing, the underlying epigenetic mechanisms are still not clear, especially in the case of human satellite cells. Here, by performing chromatin accessibility profiling (ATAC-seq) in samples isolated from human and murine muscles, we investigated the changes in the epigenetic landscape occurring during the transition from activated satellite cells to myoblasts. Our analysis identifies a compendium of putative regulatory elements defining human activated satellite cells and myoblasts, respectively. A subset of these differentially accessible loci is shared by both murine and human satellite cells, includes elements associated with known self-renewal regulators, and is enriched for motifs bound by transcription factors participating in satellite cell regulation. Integration of transcriptional and epigenetic data reveals that known regulators of metabolic gene expression, such as PPARGC1A, represent potential PAX7 targets. Through characterization of genomic networks and the underlying effectors, our data represent an important starting point for decoding and manipulating the molecular mechanisms underlying human satellite cell muscle regenerative potential.
Bibliographical noteFunding Information:
This work has been supported by a research grant from the Greg Marzolf Junior Foundation (A.M.), and a Grant-in-aid from the University of Minnesota Office of Vice President Research (A.M.). Funding for the sample acquisition was supported by the National Institutes of Health (L.S.C. 1R01DK098203). In addition, research reported in this publication was supported by the National Center for Advancing Translational Sciences of the NIH - Award Number UL1TR000114. R.C.R.P. was supported by NIH R01 AR071439 and R56 AR055299. M.K was supported by NIH R01 AR055685. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
© 2021 The Author(s)
- Human satellite cell
- Muscle stem cell
- PGC1 alpha
- Regulatory element
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't