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Cell Rep. 2016 Aug 23;16(8):2102-2115. doi: 10.1016/j.celrep.2016.07.041. Epub 2016 Aug 11.

STAT3 Regulates Self-Renewal of Adult Muscle Satellite Cells during Injury-Induced Muscle Regeneration.

Author information

1
Division of Life Science, Center for Stem Cell Research and Center for Systems Biology and Human Diseases, The State Key Lab in Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China.
2
Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
3
Division of Life Science, Center for Stem Cell Research and Center for Systems Biology and Human Diseases, The State Key Lab in Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China. Electronic address: tcheung@ust.hk.
4
Division of Life Science, Center for Stem Cell Research and Center for Systems Biology and Human Diseases, The State Key Lab in Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China. Electronic address: bczgwu@ust.hk.

Abstract

Recent studies have shown that STAT3 negatively regulates the proliferation of muscle satellite cells (MuSCs) and injury-induced muscle regeneration. These studies have been largely based on STAT3 inhibitors, which may produce off-target effects and are not cell type-specific in vivo. Here, we examine the role of STAT3 in MuSCs using two different mouse models: a MuSC-specific Stat3 knockout line and a Stat3 (MuSC-specific)/dystrophin (Dmd) double knockout (dKO) line. Stat3(-/-) MuSCs from both mutant lines were defective in proliferation. Moreover, in both mutant strains, the MuSC pool shrank, and regeneration was compromised after injury, with defects more pronounced in dKO mice along with severe muscle inflammation and fibrosis. We analyzed the transcriptomes of MuSCs from dKO and Dmd(-/-) control mice and identified multiple STAT3 target genes, including Pax7. Collectively, our work reveals a critical role of STAT3 in adult MuSCs that regulates their self-renewal during injury-induced muscle regeneration.

KEYWORDS:

Pax7; STAT3; dystrophin; fibrosis; muscle regeneration; muscle satellite cells; self-renewal

PMID:
27524611
DOI:
10.1016/j.celrep.2016.07.041
[Indexed for MEDLINE]
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