{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T07:21:19Z","timestamp":1789802479277,"version":"4.0.1"},"posted":{"date-parts":[[2026,9,16]]},"group-title":"Cell Biology","reference-count":59,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"id":[{"id":"https:\/\/ror.org\/021nxhr62","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/00knt4f32","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Loss of function of the nuclear lamina-associated protein emerin causes Emery-Dreifuss muscular dystrophy (EDMD). Efforts to define emerin\u2019s essential functions in skeletal muscle have been limited by poor concordance between mouse models and human disease phenotypes. Here, we adapt transgene-driven differentiation of human induced pluripotent stem cells (hiPSCs) into skeletal muscle (iSMs) as a tractable human model for emerin loss of function. We find that\n                  <jats:italic>EMD<\/jats:italic>\n                  knockout (KO) hiPSCs are poorly responsive to combined overexpression of MyoD and Baf60c and produce fewer mature iSMs, indicating that emerin influences muscle differentiation downstream of these differentiation factors. While MyoD acetylation and heterodimerization with E-box proteins are unaffected by emerin loss, MyoD targets including p21 and myogenin are downregulated, and\n                  <jats:italic>EMD<\/jats:italic>\n                  KO cells exhibit impaired cell cycle exit in response to differentiation signals. Transcriptomic analysis of\n                  <jats:italic>EMD<\/jats:italic>\n                  KO iSMs revealed persistent expression of cell cycle genes and decreased expression of terminal muscle differentiation genes. Dysregulated genes do not overlap with lamina-associated domains (LADs) but are instead enriched for targets of polycomb repressive complex 2 (PRC2), which deposits H3K27 trimethylation. Altogether, our data indicate a functional overlap between emerin and PRC2-mediated regulation of terminal muscle differentiation.\n                <\/jats:p>","DOI":"10.64898\/2026.09.14.750687","type":"posted-content","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T20:16:51Z","timestamp":1789589811000},"source":"Crossref","is-referenced-by-count":0,"title":["Emerin loss of function inhibits MyoD-driven differentiation of human iPSCs into skeletal myotubes"],"prefix":"10.64898","author":[{"given":"Tracy A.","family":"Knight","sequence":"first","affiliation":[{"name":"Tetrad Graduate Program, University of California, San Francisco"},{"name":"Cardiovascular Research Institute, University of California, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Mella","sequence":"additional","affiliation":[{"name":"Tetrad Graduate Program, University of California, San Francisco"},{"name":"Cardiovascular Research Institute, University of California, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodolfo S.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4064-9790","authenticated-orcid":false,"given":"Helen C.","family":"Miranda","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland OH, USA"},{"name":"Center for RNA Science and Therapeutics, Case Western Reserve University, Cleveland, OH, USA"},{"name":"Department of Neurosciences, Case Western Reserve University, Cleveland, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7181-6961","authenticated-orcid":false,"given":"Abigail","family":"Buchwalter","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, University of California, San Francisco"},{"name":"Department of Physiology, University of California, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026091823400487000_2026.09.14.750687v1.1","doi-asserted-by":"crossref","unstructured":"Puckelwartz, M. & McNally, E. 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