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

Avani Yeola; Shruthi Subramanian; Rema A. Oliver; Christine A. Lucas; Julie A.I. Thoms; Feng Yan; Jake Olivier; Diego Chacon; Melinda L. Tursky; Pallavi Srivastava; Jason R. Potas; Tzongtyng Hung; Carl Power; Philip Hardy; David D. Ma; Kristopher A. Kilian; Joshua McCarroll; Maria Kavallaris; Luke B. Hesson; Dominik Beck; David J. Curtis; Jason W.H. Wong; Edna C. Hardeman; William R. Walsh; Ralph Mobbs; Vashe Chandrakanthan; John E. Pimanda

doi:10.1126/sciadv.abd1929

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

Avani Yeola, Shruthi Subramanian, Rema A. Oliver, Christine A. Lucas, Julie A.I. Thoms, Feng Yan, Jake Olivier, Diego Chacon, Melinda L. Tursky, Pallavi Srivastava, Jason R. Potas, Tzongtyng Hung, Carl Power, Philip Hardy, David D. Ma, Kristopher A. Kilian, Joshua McCarroll, Maria Kavallaris, Luke B. Hesson, Dominik BeckDavid J. Curtis, Jason W.H. Wong, Edna C. Hardeman, William R. Walsh, Ralph Mobbs, Vashe Chandrakanthan, John E. Pimanda

Australian Centre for Blood Diseases

Research output: Contribution to journal › Article › Research › peer-review

3 Citations (Scopus)

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.

Original language	English
Article number	eabd1929
Number of pages	12
Journal	Science Advances
Volume	7
Issue number	3
DOIs	https://doi.org/10.1126/sciadv.abd1929
Publication status	Published - 13 Jan 2021

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10.1126/sciadv.abd1929Licence: CC BY-NC

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Yeola, A., Subramanian, S., Oliver, R. A., Lucas, C. A., Thoms, J. A. I., Yan, F., Olivier, J., Chacon, D., Tursky, M. L., Srivastava, P., Potas, J. R., Hung, T., Power, C., Hardy, P., Ma, D. D., Kilian, K. A., McCarroll, J., Kavallaris, M., Hesson, L. B., ... Pimanda, J. E. (2021). Induction of muscle-regenerative multipotent stem cells from human adipocytes by PDGF-AB and 5-azacytidine. Science Advances, 7(3), Article eabd1929. https://doi.org/10.1126/sciadv.abd1929

@article{33c611606f4e4230a62c5b5e8354a496,

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

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.",

author = "Avani Yeola and Shruthi Subramanian and Oliver, {Rema A.} and Lucas, {Christine A.} and Thoms, {Julie A.I.} and Feng Yan and Jake Olivier and Diego Chacon and Tursky, {Melinda L.} and Pallavi Srivastava and Potas, {Jason R.} and Tzongtyng Hung and Carl Power and Philip Hardy and Ma, {David D.} and Kilian, {Kristopher A.} and Joshua McCarroll and Maria Kavallaris and Hesson, {Luke B.} and Dominik Beck and Curtis, {David J.} and Wong, {Jason W.H.} and Hardeman, {Edna C.} and Walsh, {William R.} and Ralph Mobbs and Vashe Chandrakanthan and Pimanda, {John E.}",

year = "2021",

month = jan,

day = "13",

doi = "10.1126/sciadv.abd1929",

language = "English",

volume = "7",

journal = "Science Advances",

issn = "2375-2548",

publisher = "American Association for the Advancement of Science (AAAS)",

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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, Ma, DD, Kilian, KA, McCarroll, J, Kavallaris, M, Hesson, LB, Beck, D, Curtis, DJ, Wong, JWH, Hardeman, EC, Walsh, WR, Mobbs, R, Chandrakanthan, V & Pimanda, JE 2021, 'Induction of muscle-regenerative multipotent stem cells from human adipocytes by PDGF-AB and 5-azacytidine', Science Advances, vol. 7, no. 3, eabd1929. https://doi.org/10.1126/sciadv.abd1929

TY - JOUR

T1 - Induction of muscle-regenerative multipotent stem cells from human adipocytes by PDGF-AB and 5-azacytidine

AU - Yeola, Avani

AU - Subramanian, Shruthi

AU - Oliver, Rema A.

AU - Lucas, Christine A.

AU - Thoms, Julie A.I.

AU - Yan, Feng

AU - Olivier, Jake

AU - Chacon, Diego

AU - Tursky, Melinda L.

AU - Srivastava, Pallavi

AU - Potas, Jason R.

AU - Hung, Tzongtyng

AU - Power, Carl

AU - Hardy, Philip

AU - Ma, David D.

AU - Kilian, Kristopher A.

AU - McCarroll, Joshua

AU - Kavallaris, Maria

AU - Hesson, Luke B.

AU - Beck, Dominik

AU - Curtis, David J.

AU - Wong, Jason W.H.

AU - Hardeman, Edna C.

AU - Walsh, William R.

AU - Mobbs, Ralph

AU - Chandrakanthan, Vashe

AU - Pimanda, John E.

PY - 2021/1/13

Y1 - 2021/1/13

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85099981894&partnerID=8YFLogxK

U2 - 10.1126/sciadv.abd1929

DO - 10.1126/sciadv.abd1929

M3 - Article

C2 - 33523875

AN - SCOPUS:85099981894

SN - 2375-2548

VL - 7

JO - Science Advances

JF - Science Advances

IS - 3

M1 - eabd1929

ER -

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

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Precision nanomedicine-based diagnostics and therapeutics for refractory malignancies

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

Abstract

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Precision nanomedicine-based diagnostics and therapeutics for refractory malignancies

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