{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:28:14Z","timestamp":1791995294136,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T00:00:00Z","timestamp":1735171200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T00:00:00Z","timestamp":1735171200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000098","name":"Stem Cell Network","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000098","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":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Duchenne muscular dystrophy (DMD) is a devastating disease characterized by progressive muscle wasting that leads to diminished lifespan. In addition to the inherent weakness of dystrophin\u2010deficient muscle, the dysfunction of resident muscle stem cells (MuSC) significantly contributes to disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using the\n                      <jats:italic>mdx<\/jats:italic>\n                      mouse model of DMD, we performed an in\u2010depth characterization of disease progression and MuSC function in dystrophin\u2010deficient skeletal muscle using immunohistology, isometric force measurements, transcriptomic analysis and transplantation assays. We examined the architectural and functional changes in\n                      <jats:italic>mdx<\/jats:italic>\n                      skeletal muscle from 13 and 52\u2009weeks of age and following acute cardiotoxin (CTX) injury. We also studied MuSC dynamics and function under homeostatic conditions, during regeneration post\u2010acute injury, and following engraftment using a combination of histological and transcriptomic analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Dystrophin\u2010deficient skeletal muscle undergoes progressive changes with age and delayed regeneration in response to acute injury. Muscle hypertrophy, deposition of collagen and an increase in small myofibres occur with age in the\n                      <jats:italic>tibialis anterior<\/jats:italic>\n                      (TA) and diaphragm muscles in\n                      <jats:italic>mdx<\/jats:italic>\n                      mice. Dystrophic\n                      <jats:italic>mdx<\/jats:italic>\n                      mouse TA muscles become hypertrophic with age, whereas diaphragm atrophy is evident in 1\u2010year\u2010old\n                      <jats:italic>mdx<\/jats:italic>\n                      mice. Maximum tetanic force is comparable between genotypes in the TA, but maximum specific force is reduced by up to 38% between 13 and 52\u2009weeks in the\n                      <jats:italic>mdx<\/jats:italic>\n                      mouse. Following acute injury, myofibre hyperplasia and hypotrophy and delayed recovery of maximum tetanic force occur in the\n                      <jats:italic>mdx<\/jats:italic>\n                      TA. We also find defective MuSC polarity and reduced numbers of myocytes in\n                      <jats:italic>mdx<\/jats:italic>\n                      muscle following acute injury. We observed a 50% and 30% decrease in PAX7\n                      <jats:sup>+<\/jats:sup>\n                      and MYOG\n                      <jats:sup>+<\/jats:sup>\n                      cells, respectively, at 5\u2009days post CTX injury (5\u2009dpi) in the\n                      <jats:italic>mdx<\/jats:italic>\n                      TA. A similar decrease in\n                      <jats:italic>mdx<\/jats:italic>\n                      progenitor cell proportion is observed by single cell RNA sequencing of myogenic cells at 5\u2009dpi. The global expression of commitment\u2010related genes is also reduced at 5\u2009dpi. We find a 46% reduction in polarized PARD3 in\n                      <jats:italic>mdx<\/jats:italic>\n                      MuSCs. Finally,\n                      <jats:italic>mdx<\/jats:italic>\n                      MuSCs exhibit elevated PAX7\n                      <jats:sup>+<\/jats:sup>\n                      cell engraftment with significantly fewer donor\u2010derived myonuclei in regenerated myofibres.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study provides evidence that dystrophin deficiency in MuSCs and myofibres together contributes to progression of DMD. Ongoing muscle damage stimulates MuSC activation; however, aberrant intrinsic MuSC polarity and stem cell commitment deficits due to the loss of dystrophin impair muscle regeneration. Our study provides in\u00a0vivo validation that dystrophin\u2010deficient MuSCs undergo fewer asymmetric cell divisions, instead favouring symmetric expansion.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.13682","type":"journal-article","created":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T05:39:34Z","timestamp":1735191574000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Intrinsic Muscle Stem Cell Dysfunction Contributes to Impaired Regeneration in the\n                    <i>mdx<\/i>\n                    Mouse"],"prefix":"10.1002","volume":"16","author":[{"given":"Marie\u00a0E.","family":"Esper","sequence":"first","affiliation":[{"name":"Sprott Centre for Stem Cell Research, Regenerative Medicine Program Ottawa Hospital Research Institute  Ottawa Canada"},{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine University of Ottawa  Ottawa Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline\u00a0E.","family":"Brun","sequence":"additional","affiliation":[{"name":"Sprott Centre for Stem Cell Research, Regenerative Medicine Program Ottawa Hospital Research Institute  Ottawa Canada"},{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine University of Ottawa  Ottawa Canada"},{"name":"Institut NeuroMyoG\u00e8ne, Pathophysiology and Genetics of Neuron and Muscle, Inserm U1315, CNRS UMR5261 University Claude Bernard Lyon 1  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander\u00a0Y.\u00a0T.","family":"Lin","sequence":"additional","affiliation":[{"name":"Sprott Centre for Stem Cell Research, Regenerative Medicine Program Ottawa Hospital Research Institute  Ottawa Canada"},{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine University of Ottawa  Ottawa Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Feige","sequence":"additional","affiliation":[{"name":"Sprott Centre for Stem Cell Research, Regenerative Medicine Program Ottawa Hospital Research Institute  Ottawa Canada"},{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine University of Ottawa  Ottawa Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u00a0J.","family":"Catenacci","sequence":"additional","affiliation":[{"name":"Sprott Centre for Stem Cell Research, Regenerative Medicine Program Ottawa Hospital Research Institute  Ottawa Canada"},{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine University of Ottawa  Ottawa Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Claude","family":"Sincennes","sequence":"additional","affiliation":[{"name":"Sprott Centre for Stem Cell Research, Regenerative Medicine Program Ottawa Hospital Research Institute  Ottawa Canada"},{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine University of Ottawa  Ottawa Canada"},{"name":"Centre Armand\u2010Frappier sant\u00e9 Biotechnologie, Institut National de la Recherche Scientifique (INRS) Unit\u00e9 de recherche mixte INRS\u2010UQAC en sant\u00e9 durable  Laval Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten","family":"Ritso","sequence":"additional","affiliation":[{"name":"Sprott Centre for Stem Cell Research, Regenerative Medicine Program Ottawa Hospital Research Institute  Ottawa Canada"},{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine University of Ottawa  Ottawa Canada"},{"name":"School of Biomedical Engineering The University of British Columbia  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3866-5249","authenticated-orcid":false,"given":"Michael\u00a0A.","family":"Rudnicki","sequence":"additional","affiliation":[{"name":"Sprott Centre for Stem Cell Research, Regenerative Medicine Program Ottawa Hospital Research Institute  Ottawa Canada"},{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine University of Ottawa  Ottawa Canada"},{"name":"Department of Medicine, Faculty of Medicine University of Ottawa  Ottawa Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2023.1180980"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3990"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.018424"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2016.08.006"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2018.03.022"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(94)00276-T"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.00591.x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.07.009"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.1988.tb00866.x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1998.274.4.C1138"},{"key":"e_1_2_8_12_1","article-title":"Induction of Acute Skeletal Muscle Regeneration by Cardiotoxin Injection","volume":"119","author":"Guardiola O.","year":"2017","journal-title":"Journal of Visualized Experiments"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-48156-7"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-010-0976-6"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-020-00593-7"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2014.12.004"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.10.080"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2018391117"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13395-015-0041-y"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2014.10.007"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23158735"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/352536a0"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-31753-3"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13395-024-00344-4"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-92406-6"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/2044-5040-4-9"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-74192-9"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/2044-5040-4-10"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00128.2007"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2009.052019"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddz180"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-8966(96)00422-1"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-8966(99)00118-2"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0147198"},{"key":"e_1_2_8_35_1","first-page":"83","volume-title":"Current Topics in Developmental Biology","author":"Robertson R.","year":"2024"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010050936"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01098-y"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-30619-7"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.136095"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2019.01.002"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12899"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.13682","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcsm.13682","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.13682","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T07:32:39Z","timestamp":1775979159000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.13682"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,26]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1002\/jcsm.13682"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.13682","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,26]]},"assertion":[{"value":"2024-06-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13682"}}