Mononuclear cells from dedifferentiation of mouse myotubes display remarkable regenerative capability

Zhong Yang, Qiang Liu, Robert J. Mannix, Xiaoyin Xu, Hongli Li, Zhiyuan Ma, Donald E. Ingber, Paul D. Allen, Yaming Wang

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Certain lower organisms achieve organ regeneration by reverting differentiated cells into tissue-specific progenitors that re-enter embryonic programs. During muscle regeneration in the urodele amphibian, postmitotic multinucleated skeletal myofibers transform into mononucleated proliferating cells upon injury, and a transcription factor-msx1 plays a role in their reprograming. Whether this powerful regeneration strategy can be leveraged in mammals remains unknown, as it has not been demonstrated that the dedifferentiated progenitor cells arising from muscle cells overexpressing Msx1 are lineage-specific and possess the same potent regenerative capability as their amphibian counterparts. Here, we show that ectopic expression of Msx1 reprograms postmitotic, multinucleated, primary mouse myotubes to become proliferating mononuclear cells. These dedifferentiated cells reactivate genes expressed by embryonic muscle progenitor cells and generate only muscle tissue in vivo both in an ectopic location and inside existing muscle. More importantly, distinct from adult muscle satellite cells, these cells appear both to fuse with existing fibers and to regenerate myofibers in a robust and time-dependent manner. Upon transplantation into a degenerating muscle, these dedifferentiated cells generated a large number of myofibers that increased over time and replenished almost half of the cross-sectional area of the muscle in only 12 weeks. Our study demonstrates that mammals can harness a muscle regeneration strategy used by lower organisms when the same molecular pathway is activated. Stem Cells 2014;32:2492-2501

Original languageEnglish (US)
Pages (from-to)2492-2501
Number of pages10
JournalStem Cells
Volume32
Issue number9
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Cell Dedifferentiation
Skeletal Muscle Fibers
Regeneration
Muscles
Muscle Cells
Stem Cells
Amphibians
Mammals
Myoblasts
Transcription Factors
Transplantation
Wounds and Injuries
Genes

Keywords

  • Adult stem cells
  • Cell cycle
  • Cellular therapy
  • In vivo optical imaging
  • Muscle stem cells
  • Reprogramming
  • Skeletal muscle
  • Transcription factors

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine
  • Medicine(all)

Cite this

Yang, Z., Liu, Q., Mannix, R. J., Xu, X., Li, H., Ma, Z., ... Wang, Y. (2014). Mononuclear cells from dedifferentiation of mouse myotubes display remarkable regenerative capability. Stem Cells, 32(9), 2492-2501. https://doi.org/10.1002/stem.1742

Mononuclear cells from dedifferentiation of mouse myotubes display remarkable regenerative capability. / Yang, Zhong; Liu, Qiang; Mannix, Robert J.; Xu, Xiaoyin; Li, Hongli; Ma, Zhiyuan; Ingber, Donald E.; Allen, Paul D.; Wang, Yaming.

In: Stem Cells, Vol. 32, No. 9, 2014, p. 2492-2501.

Research output: Contribution to journalArticle

Yang, Z, Liu, Q, Mannix, RJ, Xu, X, Li, H, Ma, Z, Ingber, DE, Allen, PD & Wang, Y 2014, 'Mononuclear cells from dedifferentiation of mouse myotubes display remarkable regenerative capability', Stem Cells, vol. 32, no. 9, pp. 2492-2501. https://doi.org/10.1002/stem.1742
Yang, Zhong ; Liu, Qiang ; Mannix, Robert J. ; Xu, Xiaoyin ; Li, Hongli ; Ma, Zhiyuan ; Ingber, Donald E. ; Allen, Paul D. ; Wang, Yaming. / Mononuclear cells from dedifferentiation of mouse myotubes display remarkable regenerative capability. In: Stem Cells. 2014 ; Vol. 32, No. 9. pp. 2492-2501.
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