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DEPTOR is a stemness factor that regulates pluripotency of embryonic stem cells

Pooja Agrawal1, Joseph Reynolds1, Shereen Chew1

  • 1Buck Institute for Research on Aging, Novato, California 94945 and.

The Journal of Biological Chemistry
|September 27, 2014
PubMed

Insights

DEPTOR is a novel stemness factor that maintains embryonic stem cell (ESC) pluripotency by inhibiting the mTOR pathway. Its reduction promotes ESC differentiation, highlighting its role in stem cell self-renewal.

Area of Science:

  • Cell Biology
  • Stem Cell Biology
  • Molecular Biology

Background:

  • The mammalian target of rapamycin (mTOR) pathway is crucial for regulating stem cell functions.
  • mTOR inhibition can enhance the regenerative capacity of pluripotent stem cells.
  • DEPTOR is the sole known endogenous inhibitor of all cellular mTOR activities.

Purpose of the Study:

  • To investigate the role of DEPTOR in maintaining stem cell pluripotency and self-renewal.
  • To elucidate the mechanism by which DEPTOR influences embryonic stem cells (ESCs).

Main Methods:

  • Studied DEPTOR levels during mouse and human ESC differentiation.
  • Utilized DEPTOR knockdown experiments in mouse ESCs.
  • Assessed mTOR complex 1 activity in relation to DEPTOR levels.

Main Results:

  • DEPTOR levels significantly decrease during ESC differentiation.
  • Knockdown of DEPTOR accelerates mouse ESC differentiation.
  • Reduced DEPTOR correlates with increased mTOR complex 1 activity in differentiating ESCs.

Conclusions:

  • DEPTOR acts as a novel stemness factor promoting ESC pluripotency and self-renewal.
  • DEPTOR inhibits mTOR signaling, thereby maintaining the undifferentiated state of ESCs.
  • The DEPTOR-mTOR axis is critical for regulating stem cell fate.
Keywords:
Cell DifferentiationCell SignalingEmbryonic Stem CellMammalian Target of Rapamycin (mTOR)Neurogenesis

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