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MuSCs also retain a highly regenerative capacity and are therefore considered a promising stem cell source for regenerative therapy for muscle diseases. In this study, we identify tumor-suppressor protein Tob1 as a Pax7 target protein that negatively controls the population expansion of MuSCs. Tob1 protein is undetectable in the quiescent state but is upregulated during activation in MuSCs. Tob1 ablation in mice accelerates MuSC population expansion and boosts muscle regeneration. Moreover, inactivation of Tob1 in MuSCs ameliorates the efficiency of MuSC transplantation in a murine muscular dystrophy model. Collectively, selective targeting of Tob1 might be a therapeutic option for the treatment of muscular diseases, including muscular dystrophy and age-related sarcopenia.<\/jats:p>","DOI":"10.1242\/jcs.261886","type":"journal-article","created":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T12:51:25Z","timestamp":1721652685000},"source":"Crossref","is-referenced-by-count":1,"title":["Loss of Tob1 promotes muscle regeneration through muscle stem cell expansion"],"prefix":"10.1242","volume":"137","author":[{"given":"Yasuo","family":"Kitajima","sequence":"first","affiliation":[{"name":"Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University 1 Department of Muscle Development and Regeneration , , Kumamoto, 860-0811 , Japan"},{"name":"Graduate School of Biomedical and Health Sciences, Hiroshima University 2 Department of Immunology , , Hiroshima, 734-8551 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5472-8142","authenticated-orcid":false,"given":"Kiyoshi","family":"Yoshioka","sequence":"additional","affiliation":[{"name":"Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University 1 Department of Muscle Development and Regeneration , , Kumamoto, 860-0811 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Mikumo","sequence":"additional","affiliation":[{"name":"Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University 1 Department of Muscle Development and Regeneration , , Kumamoto, 860-0811 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun","family":"Ohki","sequence":"additional","affiliation":[{"name":"Graduate School of Biomedical and Health Sciences, Hiroshima University 2 Department of Immunology , , Hiroshima, 734-8551 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2933-5176","authenticated-orcid":false,"given":"Kazumitsu","family":"Maehara","sequence":"additional","affiliation":[{"name":"Medical Institute of Bioregulation, Kyushu University 3 Division of Transcriptomics , , Fukuoka, 812-8582 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuyuki","family":"Ohkawa","sequence":"additional","affiliation":[{"name":"Medical Institute of Bioregulation, Kyushu University 3 Division of Transcriptomics , , Fukuoka, 812-8582 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4802-7507","authenticated-orcid":false,"given":"Yusuke","family":"Ono","sequence":"additional","affiliation":[{"name":"Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University 1 Department of Muscle Development and Regeneration , , Kumamoto, 860-0811 , Japan"},{"name":"Center for Metabolic Regulation of Healthy Aging (CMHA) 4 , Faculty of Life Sciences , , Kumamoto, 860-8556 , Japan"},{"name":"Kumamoto University 4 , Faculty of Life Sciences , , Kumamoto, 860-8556 , Japan"},{"name":"Medical Research Center for High Depth Omics, Medical Institute of Bioregulation, Kyushu University 5 Division of Biological Regulation , , Fukuoka, 812-8582 , Japan"},{"name":"Research Team for Aging Science, Tokyo Metropolitan Institute for Geriatrics and Gerontology (TMIG) 6 Muscle Biology Laboratory , , Tokyo, 173-0015 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2024,8,12]]},"reference":[{"key":"2024081209473352700_JCS261886C1","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1634\/stemcells.2006-0372","article-title":"A population of myogenic stem cells that survives skeletal muscle aging","volume":"25","author":"Collins","year":"2007","journal-title":"Stem Cells"},{"key":"2024081209473352700_JCS261886C2","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1016\/j.stem.2013.07.016","article-title":"Myf5-positive satellite cells contribute to Pax7-dependent long-term maintenance of adult muscle stem cells","volume":"13","author":"Gunther","year":"2013","journal-title":"Cell Stem Cell"},{"key":"2024081209473352700_JCS261886C3","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.1038\/s41467-018-03845-1","article-title":"Histone H3.3 sub-variant H3mm7 is required for normal skeletal muscle regeneration","volume":"9","author":"Harada","year":"2018","journal-title":"Nat. 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