{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T13:06:26Z","timestamp":1784293586032,"version":"3.55.0"},"reference-count":61,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,11,6]],"date-time":"2022-11-06T00:00:00Z","timestamp":1667692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004410","name":"Scientific and Technological Research Council of Turkey","doi-asserted-by":"publisher","award":["116S307"],"award-info":[{"award-number":["116S307"]}],"id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lamina-associated polypeptide 1 (LAP1) is a ubiquitously expressed inner nuclear membrane protein encoded by TOR1AIP1, and presents as two isoforms in humans, LAP1B and LAP1C. While loss of both isoforms results in a multisystemic progeroid-like syndrome, specific loss of LAP1B causes muscular dystrophy and cardiomyopathy, suggesting that LAP1B has a critical role in striated muscle. To gain more insight into the molecular pathophysiology underlying muscular dystrophy caused by LAP1B, we established a patient-derived fibroblast line that was transdifferentiated into myogenic cells using inducible MyoD expression. Compared to the controls, we observed strongly reduced myogenic differentiation and fusion potentials. Similar defects were observed in the C2C12 murine myoblasts carrying loss-of-function LAP1A\/B mutations. Using RNA sequencing, we found that, despite MyoD overexpression and efficient cell cycle exit, transcriptional reprogramming of the LAP1B-deficient cells into the myogenic lineage is impaired with delayed activation of MYOG and muscle-specific genes. Gene set enrichment analyses suggested dysregulations of protein metabolism, extracellular matrix, and chromosome organization. Finally, we found that the LAP1B-deficient cells exhibit nuclear deformations, such as an increased number of micronuclei and altered morphometric parameters. This study uncovers the phenotypic and transcriptomic changes occurring during myoconversion of patient-derived LAP1B-deficient fibroblasts and provides a useful resource to gain insights into the mechanisms implicated in LAP1B-associated nuclear envelopathies.<\/jats:p>","DOI":"10.3390\/ijms232113615","type":"journal-article","created":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T11:56:36Z","timestamp":1667908596000},"page":"13615","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Loss of the Nuclear Envelope Protein LAP1B Disrupts the Myogenic Differentiation of Patient-Derived Fibroblasts"],"prefix":"10.3390","volume":"23","author":[{"given":"G\u00fcls\u00fcm","family":"Kayman K\u00fcrek\u00e7i","sequence":"first","affiliation":[{"name":"Department of Medical Biology, Hacettepe University Faculty of Medicine, Ankara 06100, Turkey"},{"name":"Centre Hospitalier Universitaire Sainte-Justine Research Center, Department of Molecular Biology, University of Montreal, Montreal, QC H2X 3E4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5694-8675","authenticated-orcid":false,"given":"Aybar C.","family":"Acar","sequence":"additional","affiliation":[{"name":"Cancer Systems Biology Laboratory, Graduate School of Informatics, Middle East Technical University, Ankara 06531, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pervin R.","family":"Din\u00e7er","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Hacettepe University Faculty of Medicine, Ankara 06100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ceb.2015.06.003","article-title":"Nuclear membrane diversity: Underlying tissue-specific pathologies in disease?","volume":"34","author":"Worman","year":"2015","journal-title":"Curr. 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