{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T04:28:53Z","timestamp":1789187333623,"version":"build-2803163510"},"reference-count":61,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,4,2]],"date-time":"2019-04-02T00:00:00Z","timestamp":1554163200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16H04793"],"award-info":[{"award-number":["16H04793"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Skeletal muscle satellite cells (SMSCs), the major stem cells responsible for the regeneration of skeletal muscle, are normally cell cycle arrested but differentiate to generate myocytes upon muscle damage, forming new myofibers along with self\u2010renewing stem cells in preparation for subsequent injury. In this study, we investigated which factors stimulate the proliferation and differentiation of SMSCs and found that pyruvate, the end product of glycolysis, stimulates their differentiation. Pyruvate antagonizes the effects of hypoxia on preferential self\u2010renewal of SMSCs through dephosphorylation or activation of pyruvate dehydrogenase (PDH), which mediates opening of the gateway from glycolysis to the tricarboxylic acid (TCA) cycle by producing acetyl coenzyme A from pyruvate. PDH kinase 1, highly expressed under hypoxia, is down\u2010regulated under normoxic conditions, leading to an increase in dephosphorylated PDH. Conditional deletion of PDH in SMSCs affects cell divisions generating myocytes and subsequent myotube formation, inefficient skeletal muscle regeneration upon injury, and aggravated pathogenesis of a dystrophin\u2010deficient mouse model of Duchenne muscular dystrophy. Thus, the flow from glycolysis to the TCA cycle mediated by PDH plays a pivotal role in the differentiation of SMSCs, which is critical for the progression of skeletal muscle regeneration.\u2014Hori, S., Hiramuki, Y., Nishimura, D., Sato, F., Sehara\u2010Fujisawa, A. PDH\u2010mediated metabolic flow is critical for skeletal muscle stem cell differentiation and myotube formation during regeneration in mice. FASEB J. 33, 8094\u20138109 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201802479r","type":"journal-article","created":{"date-parts":[[2019,4,2]],"date-time":"2019-04-02T18:44:34Z","timestamp":1554230674000},"page":"8094-8109","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["PDH\u2010mediated metabolic flow is critical for skeletal muscle stem cell differentiation and myotube formation during regeneration in mice"],"prefix":"10.1096","volume":"33","author":[{"given":"Shimpei","family":"Hori","sequence":"first","affiliation":[{"name":"Department of Growth Regulation Institute for Frontier Life and Medical Sciences Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Hiramuki","sequence":"additional","affiliation":[{"name":"Department of Growth Regulation Institute for Frontier Life and Medical Sciences Kyoto University  Kyoto Japan"},{"name":"Human Biology Division Fred Hutchinson Cancer Research Center  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daigo","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Department of Growth Regulation Institute for Frontier Life and Medical Sciences Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuminori","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Growth Regulation Institute for Frontier Life and Medical Sciences Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuko","family":"Sehara-Fujisawa","sequence":"additional","affiliation":[{"name":"Department of Growth Regulation Institute for Frontier Life and Medical Sciences Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.128389"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.143420"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1160809"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.02.002"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2017.02.001"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2010.07.011"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2012.10.011"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2018.05.005"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R114.563148"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-27875-3"},{"key":"e_1_2_9_12_1","doi-asserted-by":"crossref","first-page":"el3374","DOI":"10.7554\/eLife.13374","article-title":"Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation","volume":"5","author":"Zheng X.","year":"2016","journal-title":"Elife"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.08.007"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2015.09.017"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.03.044"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.11.049"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.114223"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200408066"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201488278"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2015.08.004"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature16187"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2018.03.022"},{"key":"e_1_2_9_23_1","doi-asserted-by":"crossref","unstructured":"L'honor\u00e9 A. 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