A balance between self-renewal and differentiation is critical for the regenerative capacity of tissue-resident stem cells. In skeletal muscle, successful regeneration requires the orchestrated activation, proliferation, and differentiation of muscle satellite cells (MuSCs) that are normally quiescent. A subset of MuSCs undergoes self-renewal to replenish the stem cell pool, but the features that identify and define self-renewing MuSCs remain to be elucidated. Here, through single-cell chromatin accessibility analysis, we reveal the self-renewal versus differentiation trajectories of MuSCs over the course of regeneration in vivo. We identify Betaglycan as a unique marker of self-renewing MuSCs that can be purified and efficiently contributes to regeneration after transplantation. We also show that SMAD4 and downstream genes are genetically required for self-renewal in vivo by restricting differentiation. Our study unveils the identity and mechanisms of self-renewing MuSCs, while providing a key resource for comprehensive analysis of muscle regeneration.
Single-cell chromatin accessibility profiling reveals a self-renewing muscle satellite cell state
Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Y. Diao reported “The authors declare no conflict of interest.” No other disclosures were reported.
C. Situ’s current affiliation is State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China.
Arinze E. Okafor, Xin Lin, Chenghao Situ, Xiaolin Wei, Yu Xiang, Xiuqing Wei, Zhenguo Wu, Yarui Diao; Single-cell chromatin accessibility profiling reveals a self-renewing muscle satellite cell state. J Cell Biol 7 August 2023; 222 (8): e202211073. doi: https://doi.org/10.1083/jcb.202211073
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