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dc.contributor.authorGuo, Dongsheng
dc.contributor.authorDaman, Katelyn
dc.contributor.authorChen, Jennifer Jc
dc.contributor.authorShi, Meng-Jiao
dc.contributor.authorYan, Jing
dc.contributor.authorMatijasevic, Zdenka
dc.contributor.authorMaehr, Rene
dc.contributor.authorKing, Oliver D.
dc.contributor.authorHayward, Lawrence J.
dc.contributor.authorEmerson, Charles P. Jr.
dc.date2022-08-11T08:08:34.000
dc.date.accessioned2022-08-23T15:59:40Z
dc.date.available2022-08-23T15:59:40Z
dc.date.issued2022-01-25
dc.date.submitted2022-05-05
dc.identifier.citation<p>Guo D, Daman K, Chen JJ, Shi MJ, Yan J, Matijasevic Z, Rickard AM, Bennett MH, Kiselyov A, Zhou H, Bang AG, Wagner KR, Maehr R, King OD, Hayward LJ, Emerson CP Jr. iMyoblasts for ex vivo and in vivo investigations of human myogenesis and disease modeling. Elife. 2022 Jan 25;11:e70341. doi: 10.7554/eLife.70341. PMID: 35076017; PMCID: PMC8789283. <a href="https://doi.org/10.7554/eLife.70341">Link to article on publisher's site</a></p>
dc.identifier.issn2050-084X (Linking)
dc.identifier.doi10.7554/eLife.70341
dc.identifier.pmid35076017
dc.identifier.urihttp://hdl.handle.net/20.500.14038/30723
dc.description<p>Full author list omitted for brevity. For the full list of authors, see article.</p>
dc.description.abstractSkeletal muscle myoblasts (iMyoblasts) were generated from human induced pluripotent stem cells (iPSCs) using an efficient and reliable transgene-free induction and stem cell selection protocol. Immunofluorescence, flow cytometry, qPCR, digital RNA expression profiling, and scRNA-Seq studies identify iMyoblasts as a PAX3+/MYOD1+ skeletal myogenic lineage with a fetal-like transcriptome signature, distinct from adult muscle biopsy myoblasts (bMyoblasts) and iPSC-induced muscle progenitors. iMyoblasts can be stably propagated for > 12 passages or 30 population doublings while retaining their dual commitment for myotube differentiation and regeneration of reserve cells. iMyoblasts also efficiently xenoengrafted into irradiated and injured mouse muscle where they undergo differentiation and fetal-adult MYH isoform switching, demonstrating their regulatory plasticity for adult muscle maturation in response to signals in the host muscle. Xenograft muscle retains PAX3+ muscle progenitors and can regenerate human muscle in response to secondary injury. As models of disease, iMyoblasts from individuals with Facioscapulohumeral Muscular Dystrophy revealed a previously unknown epigenetic regulatory mechanism controlling developmental expression of the pathological DUX4 gene. iMyoblasts from Limb-Girdle Muscular Dystrophy R7 and R9 and Walker Warburg Syndrome patients modeled their molecular disease pathologies and were responsive to small molecule and gene editing therapeutics. These findings establish the utility of iMyoblasts for ex vivo and in vivo investigations of human myogenesis and disease pathogenesis and for the development of muscle stem cell therapeutics.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=35076017&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsCopyright © 2022, Guo et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectdevelopmental biology
dc.subjecthuman
dc.subjecthuman ipsc myogenesis
dc.subjectiMyoblasts
dc.subjectmouse
dc.subjectmuscle stem cells
dc.subjectregenerative medicine
dc.subjectstem cells
dc.subjectxenograft
dc.subjectCell Biology
dc.subjectCellular and Molecular Physiology
dc.subjectCongenital, Hereditary, and Neonatal Diseases and Abnormalities
dc.subjectDevelopmental Biology
dc.subjectDisease Modeling
dc.subjectMusculoskeletal Diseases
dc.subjectNervous System Diseases
dc.titleiMyoblasts for ex vivo and in vivo investigations of human myogenesis and disease modeling
dc.typeJournal Article
dc.source.journaltitleeLife
dc.source.volume11
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3227&amp;context=faculty_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/2194
dc.identifier.contextkey29018201
refterms.dateFOA2022-08-23T15:59:40Z
html.description.abstract<p>Skeletal muscle myoblasts (iMyoblasts) were generated from human induced pluripotent stem cells (iPSCs) using an efficient and reliable transgene-free induction and stem cell selection protocol. Immunofluorescence, flow cytometry, qPCR, digital RNA expression profiling, and scRNA-Seq studies identify iMyoblasts as a PAX3+/MYOD1+ skeletal myogenic lineage with a fetal-like transcriptome signature, distinct from adult muscle biopsy myoblasts (bMyoblasts) and iPSC-induced muscle progenitors. iMyoblasts can be stably propagated for > 12 passages or 30 population doublings while retaining their dual commitment for myotube differentiation and regeneration of reserve cells. iMyoblasts also efficiently xenoengrafted into irradiated and injured mouse muscle where they undergo differentiation and fetal-adult MYH isoform switching, demonstrating their regulatory plasticity for adult muscle maturation in response to signals in the host muscle. Xenograft muscle retains PAX3+ muscle progenitors and can regenerate human muscle in response to secondary injury. As models of disease, iMyoblasts from individuals with Facioscapulohumeral Muscular Dystrophy revealed a previously unknown epigenetic regulatory mechanism controlling developmental expression of the pathological DUX4 gene. iMyoblasts from Limb-Girdle Muscular Dystrophy R7 and R9 and Walker Warburg Syndrome patients modeled their molecular disease pathologies and were responsive to small molecule and gene editing therapeutics. These findings establish the utility of iMyoblasts for ex vivo and in vivo investigations of human myogenesis and disease pathogenesis and for the development of muscle stem cell therapeutics.</p>
dc.identifier.submissionpathfaculty_pubs/2194
dc.contributor.departmentEmerson Lab
dc.contributor.departmentKing Lab
dc.contributor.departmentProgram in Molecular Medicine
dc.contributor.departmentTransgenic Animal Modeling Core
dc.contributor.departmentLi Weibo Institute for Rare Disease Research
dc.contributor.departmentDepartment of Neurology
dc.contributor.departmentWellstone Muscular Dystrophy Program
dc.source.pagese70341


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Copyright © 2022, Guo et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Except where otherwise noted, this item's license is described as Copyright © 2022, Guo et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.