{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:17:51Z","timestamp":1788520671553,"version":"build-2803163510"},"reference-count":71,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/100005716","name":"National Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005716","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Formation of skeletal muscle is among the most striking examples of cellular plasticity in animal tissue development, where muscle progenitor cells are reprogrammed by epithelial-mesenchymal transition (EMT) to produce multinucleated myofibers. The regulation of EMT in muscle formation remains poorly understood. Here, we demonstrate that the long noncoding RNA (lncRNA) Meg3 regulates EMT in myoblast differentiation and skeletal muscle regeneration. Chronic inhibition of Meg3 in C2C12 myoblasts induced EMT, and suppressed cell state transitions required for differentiation. Furthermore, adenoviral Meg3 knockdown compromised muscle regeneration, which was accompanied by abnormal mesenchymal gene expression and interstitial cell proliferation. Transcriptomic and pathway analyses of Meg3-depleted C2C12 myoblasts and injured skeletal muscle revealed a significant dysregulation of EMT-related genes, and identified TGF\u03b2 as a key upstream regulator. Importantly, inhibition of TGF\u03b2R1 and its downstream effectors, and the EMT transcription factor Snai2, restored many aspects of myogenic differentiation in Meg3-depleted myoblasts in vitro. We further demonstrate that reduction of Meg3-dependent Ezh2 activity results in epigenetic alterations associated with TGF\u03b2 activation. Thus, Meg3 regulates myoblast identity to maintain proper cell state for progression into differentiation.<\/jats:p>","DOI":"10.1242\/dev.194027","type":"journal-article","created":{"date-parts":[[2020,12,9]],"date-time":"2020-12-09T11:41:33Z","timestamp":1607514093000},"source":"Crossref","is-referenced-by-count":21,"title":["The long noncoding RNA\n                    <i>Meg3<\/i>\n                    regulates myoblast plasticity and muscle regeneration through epithelial-mesenchymal transition"],"prefix":"10.1242","author":[{"given":"Tiffany L.","family":"Dill","sequence":"first","affiliation":[{"name":"Department of Biology, Program in Cell and Molecular Biology, Boston University, Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Carroll","sequence":"additional","affiliation":[{"name":"Department of Biology, Program in Cell and Molecular Biology, Boston University, Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Pinheiro","sequence":"additional","affiliation":[{"name":"Department of Biology, Program in Cell and Molecular Biology, Boston University, Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiachen","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Biology, Program in Cell and Molecular Biology, Boston University, Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5643-2345","authenticated-orcid":false,"given":"Francisco J.","family":"Naya","sequence":"additional","affiliation":[{"name":"Department of Biology, Program in Cell and Molecular Biology, Boston University, Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2020,1,1]]},"reference":[{"key":"2021042623001965100_DEV194027C1","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1111\/j.1474-9728.2004.00135.x","article-title":"Alterations in the TGF\u03b2 signaling pathway in myogenic progenitors with age","volume":"3","author":"Beggs","year":"2004","journal-title":"Aging Cell."},{"key":"2021042623001965100_DEV194027C2","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1007\/s00018-012-1080-8","article-title":"The microRNAs within the DLK1-DIO3 genomic region: involvement in disease pathogenesis","volume":"70","author":"Benetatos","year":"2013","journal-title":"Cell. 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