title: STAT3 Regulates Self-Renewal of Adult Muscle Satellite Cells during Injury-Induced Muscle Regeneration.
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.
authors.affiliation: 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.
authors.forename: Han
authors.initials: H
authors.lastname: Zhu
authors.affiliation: 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.
authors.forename: Fang
authors.initials: F
authors.lastname: Xiao
authors.affiliation: 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.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Wei
authors.affiliation: 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.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: 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.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.affiliation: 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.
authors.forename: Haixia
authors.initials: H
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Yarui
authors.initials: Y
authors.lastname: Diao
authors.affiliation: Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Huating
authors.initials: H
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Nancy Y
authors.initials: NY
authors.lastname: Ip
authors.affiliation: 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.
authors.forename: Tom H
authors.initials: TH
authors.lastname: Cheung
authors.affiliation: 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.
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Wu
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D016189:Dystrophin / Q000172:deficiency* / Q000235:genetics; D005355:Fibrosis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D009220:Myositis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051763:PAX7 Transcription Factor / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000172:deficiency* / Q000235:genetics; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D016189:Dystrophin; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C085339:apo-dystrophin 1
keywords: Pax7; STAT3; dystrophin; fibrosis; muscle regeneration; muscle satellite cells; self-renewal