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dc.contributor.authorSun, C.
dc.contributor.authorChoi, I.Y.
dc.contributor.authorLovering, R.M.
dc.date.accessioned2020-06-16T19:54:21Z
dc.date.available2020-06-16T19:54:21Z
dc.date.issued2020
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85085961759&doi=10.1172%2fjci.insight.134287&partnerID=40&md5=5099853803723ca5519dbe8007a0af44
dc.identifier.urihttp://hdl.handle.net/10713/13082
dc.description.abstractDuchenne muscular dystrophy (DMD) is the most common muscular dystrophy. In the present study, when human induced pluripotent stem cells (hiPSCs) were differentiated into myoblasts, the myoblasts derived from DMD patient hiPSCs (DMD hiPSC-derived myoblasts) exhibited an identifiable DMD-relevant phenotype: myogenic fusion deficiency. Based on this model, we developed a DMD hiPSC-derived myoblast screening platform employing a high-content imaging (BD Pathway 855) approach to generate parameters describing morphological as well as myogenic marker protein expression. Following treatment of the cells with 1524 compounds from the Johns Hopkins Clinical Compound Library, compounds that enhanced myogenic fusion of DMD hiPSC-derived myoblasts were identified. The final hits were ginsenoside Rd and fenofibrate. Transcriptional profiling revealed that ginsenoside Rd is functionally related to FLT3 signaling, while fenofibrate is linked to TGF-? signaling. Preclinical tests in mdx mice showed that treatment with these 2 hit compounds can significantly ameliorate some of the skeletal muscle phenotypes caused by dystrophin deficiency, supporting their therapeutic potential. Further study revealed that fenofibrate could inhibit mitochondrion-induced apoptosis in DMD hiPSC-derived cardiomyocytes. We have developed a platform based on DMD hiPSC-derived myoblasts for drug screening and identified 2 promising small molecules with in vivo efficacy.en_US
dc.description.urihttps://doi.org/10.1172/jci.insight.134287en_US
dc.language.isoen_USen_US
dc.publisherThe American Society for Clinical Investigationen_US
dc.relation.ispartofJCI insight
dc.subjectHuman stem cellsen_US
dc.subjectMuscle Biologyen_US
dc.subjectSkeletal muscleen_US
dc.subjectStem cellsen_US
dc.titleDuchenne muscular dystrophy hiPSC-derived myoblast drug screen identifies compounds that ameliorate disease in mdx miceen_US
dc.typeArticleen_US
dc.identifier.doi10.1172/jci.insight.134287
dc.identifier.pmid32343677


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