{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T10:29:51Z","timestamp":1792664991592,"version":"4.5.0"},"reference-count":32,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T00:00:00Z","timestamp":1625011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017R1C1B3009321"],"award-info":[{"award-number":["2017R1C1B3009321"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017M3C7A1047640"],"award-info":[{"award-number":["2017M3C7A1047640"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR070751"],"award-info":[{"award-number":["AR070751"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Understanding the signaling pathways that regulate the final differentiation of human myoblasts is essential for successful cell transplantation and drug screening for the treatment of muscular dystrophy. In an effort to improve myotube formation from hiPSC-derived myoblasts, we validated a collection of 13 small molecules in a newly established in vitro screening platform for the assessment of myotube formation. The analysis of myotube formation as measured by the fusion index showed that the combinational inhibition of the TGF\u03b2 signaling with NOTCH signaling enhances the ability of multi-nucleated myotube production. Combinational treatment of inhibitors for TGF\u03b2 and NOTCH signaling pathways improved myotube formation in a dose-dependent manner. This effect was achieved by inhibiting the combinatorial mechanism of signaling. The combination treatment of small molecules effective in inducing multinucleated myotubes was validated in healthy human primary myoblasts. In addition, it was also applied to DMD patient iPSC-derived myoblasts to enhance the generation of multinucleated myotubes.<\/jats:p>","DOI":"10.3390\/cells10071649","type":"journal-article","created":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T02:44:39Z","timestamp":1625107479000},"page":"1649","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Inhibition of the Combinatorial Signaling of Transforming Growth Factor-Beta and NOTCH Promotes Myotube Formation of Human Pluripotent Stem Cell-Derived Skeletal Muscle Progenitor Cells"],"prefix":"10.3390","volume":"10","author":[{"given":"In Young","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho Tae","family":"Lim","sequence":"additional","affiliation":[{"name":"The Institute for Cell Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Hyun","family":"Che","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabsang","family":"Lee","sequence":"additional","affiliation":[{"name":"The Institute for Cell Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA"},{"name":"Department of Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA"},{"name":"The Solomon H. Snyder Department of Neuroscience, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5374-712X","authenticated-orcid":false,"given":"Yong Jun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea"},{"name":"Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Korea"},{"name":"Department of Pathology, College of Medicine, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1152\/physrev.00019.2003","article-title":"Cellular and molecular regulation of muscle regeneration","volume":"84","author":"Charge","year":"2004","journal-title":"Physiol. 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