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Slow Your Roll: Inhibiting SETD7 Activity Permits Ex Vivo Expansion of Muscle Stem Cells

Ryo Fujita1, Colin Crist1

  • 1Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada; Department of Human Genetics, McGill University, Montreal, QC, Canada.

Cell Stem Cell
|February 4, 2018
PubMed

Insights

Inhibition of cytoplasmic SETD7, a lysine methyltransferase, expands naive muscle stem cells. This finding helps preserve stem cell regenerative capacity during ex vivo culture for potential therapeutic applications.

Area of Science:

  • Muscle stem cell biology
  • Epigenetics
  • Cellular regenerative capacity

Background:

  • Muscle stem cells (MuSCs) are crucial for muscle regeneration.
  • Ex vivo culture leads to rapid loss of MuSC regenerative potential.
  • Maintaining MuSC identity during culture is a significant challenge.

Purpose of the Study:

  • To identify molecular targets that can preserve MuSC identity and function during ex vivo culture.
  • To investigate the role of cytoplasmic lysine methyltransferases in regulating MuSC fate.

Main Methods:

  • Utilized mouse and human muscle stem cells.
  • Employed genetic and pharmacological inhibition of cytoplasmic SETD7 (lysine methyltransferase).
  • Assessed stem cell expansion, differentiation status, and myogenic progression.

Main Results:

  • Inhibition of cytoplasmic SETD7 significantly expanded naive, undifferentiated mouse and human muscle stem cells.
  • SETD7 inhibition restricted the progression of muscle stem cells through the myogenic program.
  • Preserved stem cell populations maintained their undifferentiated state.

Conclusions:

  • Cytoplasmic SETD7 is a key regulator of muscle stem cell differentiation.
  • Targeting SETD7 offers a promising strategy to enhance muscle stem cell expansion ex vivo.
  • This approach could improve the efficacy of cell-based therapies for muscle disorders.

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