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DDIT4 regulates mesenchymal stem cell fate by mediating between HIF1α and mTOR signalling

Borzo Gharibi1, Mandeep Ghuman1, Francis J Hughes1

  • 1Division of Tissue Engineering and Biophotonics, Dental Institute, King's College London, Tower Wing, Guy's Hospital, London, SE1 9RT. UK.

Scientific Reports
|November 24, 2016
PubMed

Insights

DNA Damage Inducible Transcript 4 (DDIT4) links HIF1α and mTOR signaling to control adult stem cell fate. This discovery reveals how DDIT4 regulates stem cell self-renewal and differentiation.

Area of Science:

  • Stem cell biology
  • Molecular signaling pathways
  • Adult stem cell homeostasis

Background:

  • Stem cell fate is determined by external cues and internal pathways.
  • Understanding the molecular mechanisms governing stem cell self-renewal and differentiation is crucial.

Purpose of the Study:

  • To investigate the role of DNA Damage Inducible Transcript 4 (DDIT4) in adult stem cell fate.
  • To elucidate the connection between DDIT4, HIF1α, and mTOR signaling in stem cell regulation.

Main Methods:

  • Global gene expression analysis of mesenchymal stem cells (MSCs).
  • Live RNA cell sorting and single-clone derivation.
  • Loss-of-function and gain-of-function experiments.

Main Results:

  • DDIT4 expression correlates with MSC differentiation potential.
  • DDIT4 regulates mTOR signaling, pluripotency gene expression, and differentiation.
  • DDIT4 acts downstream of HIF1α in regulating stem cell fate.

Conclusions:

  • DDIT4 serves as a critical link between HIF1α and mTOR signaling pathways.
  • DDIT4 plays a key role in coordinating stem cell self-renewal and differentiation.
  • Findings offer insights into adult stem cell homeostasis regulation.

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