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A Molecular Switch Regulating Cell Fate Choice between Muscle Progenitor Cells and Brown Adipocytes.

Publication ,  Journal Article
An, Y; Wang, G; Diao, Y; Long, Y; Fu, X; Weng, M; Zhou, L; Sun, K; Cheung, TH; Ip, NY; Sun, H; Wang, H; Wu, Z
Published in: Dev Cell
May 22, 2017

During mouse embryo development, both muscle progenitor cells (MPCs) and brown adipocytes (BAs) are known to derive from the same Pax7+/Myf5+ progenitor cells. However, the underlying mechanisms for the cell fate control remain unclear. In Pax7-null MPCs from young mice, several BA-specific genes, including Prdm16 and Ucp1 and many other adipocyte-related genes, were upregulated with a concomitant reduction of Myod and Myf5, two muscle lineage-determining genes. This suggests a cell fate switch from MPC to BA. Consistently, freshly isolated Pax7-null but not wild-type MPCs formed lipid-droplet-containing UCP1+ BA in culture. Mechanistically, MyoD and Myf5, both known transcription targets of Pax7 in MPC, potently repress Prdm16, a BA-specific lineage-determining gene, via the E2F4/p107/p130 transcription repressor complex. Importantly, inducible Pax7 ablation in developing mouse embryos promoted brown fat development. Thus, the MyoD/Myf5-E2F4/p107/p130 axis functions in both the Pax7+/Myf5+ embryonic progenitor cells and postnatal myoblasts to repress the alternative BA fate.

Duke Scholars

Published In

Dev Cell

DOI

EISSN

1878-1551

Publication Date

May 22, 2017

Volume

41

Issue

4

Start / End Page

382 / 391.e5

Location

United States

Related Subject Headings

  • Up-Regulation
  • Transcription, Genetic
  • Transcription Factors
  • Stem Cells
  • Repressor Proteins
  • PAX7 Transcription Factor
  • Myogenic Regulatory Factor 5
  • MyoD Protein
  • Muscles
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
An, Y., Wang, G., Diao, Y., Long, Y., Fu, X., Weng, M., … Wu, Z. (2017). A Molecular Switch Regulating Cell Fate Choice between Muscle Progenitor Cells and Brown Adipocytes. Dev Cell, 41(4), 382-391.e5. https://doi.org/10.1016/j.devcel.2017.04.012
Journal cover image

Published In

Dev Cell

DOI

EISSN

1878-1551

Publication Date

May 22, 2017

Volume

41

Issue

4

Start / End Page

382 / 391.e5

Location

United States

Related Subject Headings

  • Up-Regulation
  • Transcription, Genetic
  • Transcription Factors
  • Stem Cells
  • Repressor Proteins
  • PAX7 Transcription Factor
  • Myogenic Regulatory Factor 5
  • MyoD Protein
  • Muscles
  • Mice