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

Yeola, A; Subramanian, S; Oliver, RA; Lucas, CA; Thoms, JAI; Yan, F; Olivier, J; Chacon, D; Tursky, ML; Srivastava, P; Potas, JR; Hung, T; Power, C; Hardy, P; D., D; Kilian, KA; McCarroll, J; Kavallaris, M; Hesson, LB; Beck, D; Curtis, DJ; Wong, JWH; Hardeman, EC; Walsh, WR; Mobbs, R; Chandrakanthan, V; Pimanda, JE

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

Yeola, A Subramanian, S Oliver, RA Lucas, CA Thoms, JAI Yan, F Olivier, J Chacon, D Tursky, ML Srivastava, P Potas, JR Hung, T Power, C Hardy, P D., D Kilian, KA McCarroll, J Kavallaris, M Hesson, LB Beck, D Curtis, DJ Wong, JWH Hardeman, EC Walsh, WR Mobbs, R Chandrakanthan, V Pimanda, JE

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Publisher:: American Association for the Advancement of Science
Publication Type:: Journal Article
Citation:: Science Advances, 2021, 7, (3), pp. 1-12
Issue Date:: 2021-01-13

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Field	Value	Language
dc.contributor.author	Yeola, A
dc.contributor.author	Subramanian, S
dc.contributor.author	Oliver, RA
dc.contributor.author	Lucas, CA
dc.contributor.author	Thoms, JAI
dc.contributor.author	Yan, F
dc.contributor.author	Olivier, J
dc.contributor.author	Chacon, D
dc.contributor.author	Tursky, ML
dc.contributor.author	Srivastava, P
dc.contributor.author	Potas, JR
dc.contributor.author	Hung, T
dc.contributor.author	Power, C
dc.contributor.author	Hardy, P
dc.contributor.author	D., D
dc.contributor.author	Kilian, KA
dc.contributor.author	McCarroll, J
dc.contributor.author	Kavallaris, M
dc.contributor.author	Hesson, LB
dc.contributor.author	Beck, D
dc.contributor.author	Curtis, DJ
dc.contributor.author	Wong, JWH
dc.contributor.author	Hardeman, EC
dc.contributor.author	Walsh, WR
dc.contributor.author	Mobbs, R
dc.contributor.author	Chandrakanthan, V
dc.contributor.author	Pimanda, JE
dc.date.accessioned	2022-03-08T03:42:09Z
dc.date.available	2020-11-23
dc.date.available	2022-03-08T03:42:09Z
dc.date.issued	2021-01-13
dc.identifier.citation	Science Advances, 2021, 7, (3), pp. 1-12
dc.identifier.issn	2375-2548
dc.identifier.issn	2375-2548
dc.identifier.uri	http://hdl.handle.net/10453/155052
dc.description.abstract	Terminally 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.format	Electronic-Print
dc.language	eng
dc.publisher	American Association for the Advancement of Science
dc.relation	University of Technology Sydney
dc.relation	Anthony Rothe Memorial Trust
dc.relation	Cancer Institute NSW
dc.relation	Gilead Sciences Pty Ltd
dc.relation	Cancer Australia1100978
dc.relation.ispartof	Science Advances
dc.relation.isbasedon	10.1126/sciadv.abd1929
dc.rights	info:eu-repo/semantics/openAccess
dc.title	Induction of muscle-regenerative multipotent stem cells from human adipocytes by PDGF-AB and 5-azacytidine
dc.type	Journal Article
utslib.citation.volume	7
utslib.location.activity	United States
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Strength - AAI - Advanced Analytics Institute Research Centre
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
utslib.copyright.status	open_access	*
pubs.consider-herdc	false
dc.date.updated	2022-03-08T03:42:01Z
pubs.issue	3
pubs.publication-status	Published
pubs.volume	7
utslib.citation.issue	3

Abstract:

Terminally 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.

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http://hdl.handle.net/10453/155052