{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:53:36Z","timestamp":1790805216608,"version":"4.1.0"},"reference-count":105,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,2,14]],"date-time":"2021-02-14T00:00:00Z","timestamp":1613260800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004923","name":"AFM-T\u00e9l\u00e9thon","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014865","name":"Fondation Maladies Rares","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Duchenne muscular dystrophy (DMD) causes severe disability of children and death of young men, with an incidence of approximately 1\/5000 male births. Symptoms appear in early childhood, with a diagnosis made mostly around 4\u00a0years old, a time where the amount of muscle damage is already significant, preventing early therapeutic interventions that could be more efficient at halting disease progression. In the meantime, the precise moment at which disease phenotypes arise\u2014even asymptomatically\u2014is still unknown. Thus, there is a critical need to better define DMD onset as well as its first manifestations, which could help identify early disease biomarkers and novel therapeutic targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We have used both human tissue\u2010derived myoblasts and human induced pluripotent stem cells (hiPSCs) from DMD patients to model skeletal myogenesis and compared their differentiation dynamics with that of healthy control cells by a comprehensive multi\u2010omic analysis at seven time points. Results were strengthened with the analysis of isogenic CRISPR\u2010edited human embryonic stem cells and through comparisons against published transcriptomic and proteomic datasets from human DMD muscles. The study was completed with DMD knockdown\/rescue experiments in hiPSC\u2010derived skeletal muscle progenitor cells and adenosine triphosphate measurement in hiPSC\u2010derived myotubes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Transcriptome and miRnome comparisons combined with protein analyses demonstrated that hiPSC differentiation (i) leads to embryonic\/foetal myotubes that mimic described DMD phenotypes at the differentiation endpoint and (ii) homogeneously and robustly recapitulates key developmental steps\u2014mesoderm, somite, and skeletal muscle. Starting at the somite stage, DMD dysregulations concerned almost 10% of the transcriptome. These include mitochondrial genes whose dysregulations escalate during differentiation. We also describe fibrosis as an intrinsic feature of DMD skeletal muscle cells that begins early during myogenesis. All the omics data are available online for exploration through a graphical interface at\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/muscle-dmd.omics.ovh\/\">https:\/\/muscle\u2010dmd.omics.ovh\/<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our data argue for an early developmental manifestation of DMD whose onset is triggered before the entry into the skeletal muscle compartment, data leading to a necessary reconsideration of dystrophin roles during muscle development. This hiPSC model of skeletal muscle differentiation offers the possibility to explore these functions as well as find earlier DMD biomarkers and therapeutic targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.12665","type":"journal-article","created":{"date-parts":[[2021,2,17]],"date-time":"2021-02-17T12:32:55Z","timestamp":1613565175000},"page":"209-232","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Myogenesis modelled by human pluripotent stem cells: a multi\u2010omic study of Duchenne myopathy early onset"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6557-4190","authenticated-orcid":false,"given":"Virginie","family":"Mournetas","sequence":"first","affiliation":[{"name":"INSERM UEVE UMR861, I\u2010STEM, AFM  Corbeil\u2010Essonnes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9829-5008","authenticated-orcid":false,"given":"Emmanuelle","family":"Massourid\u00e8s","sequence":"additional","affiliation":[{"name":"CECS, I\u2010STEM, AFM  Corbeil\u2010Essonnes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5706-8178","authenticated-orcid":false,"given":"Jean\u2010Baptiste","family":"Dupont","sequence":"additional","affiliation":[{"name":"INSERM UEVE UMR861, I\u2010STEM, AFM  Corbeil\u2010Essonnes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7712-8270","authenticated-orcid":false,"given":"Etienne","family":"Kornobis","sequence":"additional","affiliation":[{"name":"Biomics, C2RT Institut Pasteur  Paris France"},{"name":"Hub de Bioinformatique et Biostatistique \u2010 D\u00e9partement BiologieComputationnelle  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5601-3498","authenticated-orcid":false,"given":"H\u00e9l\u00e8ne","family":"Polv\u00e8che","sequence":"additional","affiliation":[{"name":"CECS, I\u2010STEM, AFM  Corbeil\u2010Essonnes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5877-2615","authenticated-orcid":false,"given":"Margot","family":"Jarrige","sequence":"additional","affiliation":[{"name":"CECS, I\u2010STEM, AFM  Corbeil\u2010Essonnes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6783-5772","authenticated-orcid":false,"given":"Alan R.L.","family":"Dorval","sequence":"additional","affiliation":[{"name":"CECS, I\u2010STEM, AFM  Corbeil\u2010Essonnes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8916-0953","authenticated-orcid":false,"given":"Maxime R.F.","family":"Gosselin","sequence":"additional","affiliation":[{"name":"Molecular Medicine, School of Pharmacy and Biomedical Sciences University of Portsmouth  Portsmouth UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5028-1865","authenticated-orcid":false,"given":"Antigoni","family":"Manousopoulou","sequence":"additional","affiliation":[{"name":"Department of Immuno\u2010Oncology Beckman Research Institute, City of Hope National Medical Center  Duarte CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1050-0805","authenticated-orcid":false,"given":"Spiros D.","family":"Garbis","sequence":"additional","affiliation":[{"name":"Unit for Cancer Sciences, Centre for Proteomics Research, Institute for Life Sciences University of Southampton  Southampton UK"},{"name":"Proteas Bioanalytics Inc. 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