Single-cell chromatin accessibility profiling reveals a self-renewing muscle satellite cell state

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 quiesce...

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Veröffentlicht in:The Journal of cell biology 2023-08, Vol.222 (8), p.1
Hauptverfasser: Okafor, Arinze E, Lin, Xin, Situ, Chenghao, Wei, Xiaolin, Xiang, Yu, Wei, Xiuqing, Wu, Zhenguo, Diao, Yarui
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container_issue 8
container_start_page 1
container_title The Journal of cell biology
container_volume 222
creator Okafor, Arinze E
Lin, Xin
Situ, Chenghao
Wei, Xiaolin
Xiang, Yu
Wei, Xiuqing
Wu, Zhenguo
Diao, Yarui
description 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.
doi_str_mv 10.1083/jcb.202211073
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subjects Accessibility
Cell Cycle and Division
Cell Differentiation
Cell Division
Cell proliferation
Cell self-renewal
Chromatin
Chromatin - genetics
Chromatin or Epigenetics
Development
Differentiation
In vivo methods and tests
Muscle, Skeletal
Muscles
Regeneration
Satellite cells
Satellite Cells, Skeletal Muscle
Skeletal muscle
Smad4 protein
Stem Cells
Transplantation
title Single-cell chromatin accessibility profiling reveals a self-renewing muscle satellite cell state
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