Induction of muscle-regenerative multipotent stem cells from human adipocytes by PDGF-AB and 5-azacytidine

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dc.contributor.authorYeola, A.
dc.contributor.authorSubramanian, S.
dc.contributor.authorOliver, R.A.
dc.contributor.authorLucas, C.A.
dc.contributor.authorThoms, J.A.I.
dc.contributor.authorYan, F.
dc.contributor.authorOlivier, J.
dc.contributor.authorChacon, D.
dc.contributor.authorTursky, M.L.
dc.contributor.authorSrivastava, P.
dc.contributor.authorPotas, J.R.
dc.contributor.authorHung, T.
dc.contributor.authorPower, C.
dc.contributor.authorHardy, P.
dc.contributor.authorMa, D.D.
dc.contributor.authorKilian, K.A.
dc.contributor.authorMcCarroll, J.
dc.contributor.authorKavallaris, M.
dc.contributor.authorHesson, L.B.
dc.contributor.authorBeck, D.
dc.contributor.authoret al.
dc.date.issued2021
dc.description.abstractTerminally differentiated murine osteocytes and adipocytes can be reprogrammed using platelet-derived growth factor-AB and 5-azacytidine into multipotent stem cells with stromal cell characteristics. We have now optimized culture conditions to reprogram human adipocytes into induced multipotent stem (iMS) cells and characterized their molecular and functional properties. Although the basal transcriptomes of adipocyte-derived iMS cells and adipose tissue-derived mesenchymal stem cells were similar, there were changes in histone modifications and CpG methylation at cis-regulatory regions consistent with an epigenetic landscape that was primed for tissue development and differentiation. In a non-specific tissue injury xenograft model, iMS cells contributed directly to muscle, bone, cartilage, and blood vessels, with no evidence of teratogenic potential. In a cardiotoxin muscle injury model, iMS cells contributed specifically to satellite cells and myofibers without ectopic tissue formation. Together, human adipocyte-derived iMS cells regenerate tissues in a context-dependent manner without ectopic or neoplastic growth.
dc.description.statementofresponsibilityAvani Yeola ... Vashe Chandrakanthan ... et al.
dc.identifier.citationScience Advances, 2021; 7(3):eabd1929-1-eabd1929-12
dc.identifier.doi10.1126/sciadv.abd1929
dc.identifier.issn2375-2548
dc.identifier.issn2375-2548
dc.identifier.orcidChandrakanthan, V. [0000-0002-4314-5029]
dc.identifier.urihttps://hdl.handle.net/2440/140761
dc.language.isoen
dc.publisherAmerican Association for the Advancement of Science (AAAS)
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1119152
dc.relation.granthttp://purl.org/au-research/grants/arc/FT180100417
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1091261
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1139811
dc.rights© 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S.Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
dc.source.urihttps://doi.org/10.1126/sciadv.abd1929
dc.subjectAdipocytes
dc.subjectAdipose Tissue
dc.subjectAnimals
dc.subjectAzacitidine
dc.subjectCell Differentiation
dc.subjectCells, Cultured
dc.subjectHumans
dc.subjectMice
dc.subjectMultipotent Stem Cells
dc.subjectMuscles
dc.subjectPlatelet-Derived Growth Factor
dc.subject.meshMuscles
dc.subject.meshAdipose Tissue
dc.subject.meshCells, Cultured
dc.subject.meshAdipocytes
dc.subject.meshMultipotent Stem Cells
dc.subject.meshAnimals
dc.subject.meshHumans
dc.subject.meshMice
dc.subject.meshAzacitidine
dc.subject.meshPlatelet-Derived Growth Factor
dc.subject.meshCell Differentiation
dc.titleInduction of muscle-regenerative multipotent stem cells from human adipocytes by PDGF-AB and 5-azacytidine
dc.typeJournal article
pubs.publication-statusPublished

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