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An elaborate regulation of Mammalian target of rapamycin activity is required for somatic cell reprogramming induced

Jing He1, Lan Kang, Tong Wu

  • 1National Institute of Biological Sciences (NIBS), Beijing, People's Republic of China.

Stem Cells and Development
|April 5, 2012
PubMed

Insights

Precise regulation of the mammalian target of the rapamycin (mTOR) pathway is crucial for reprogramming somatic cells into induced pluripotent stem (iPS) cells. Both excessive activation and complete blockage of mTOR inhibit this critical cellular reprogramming process.

Area of Science:

  • Cell Biology
  • Stem Cell Research
  • Molecular Signaling

Background:

  • The mammalian target of the rapamycin (mTOR) pathway regulates fundamental cellular processes like growth and survival.
  • Recent breakthroughs allow direct reprogramming of somatic cells to pluripotency using transcription factors.
  • The role of the mTOR pathway in somatic cell reprogramming remained largely unexplored.

Purpose of the Study:

  • To investigate the involvement and regulatory role of the mTOR signaling pathway in somatic cell reprogramming to pluripotency.
  • To determine if specific mTOR activity levels are necessary for successful induced pluripotent stem (iPS) cell generation.

Main Methods:

  • Utilized somatic cells from Tsc2(-/-) embryos with hyperactivated mTOR.
  • Employed a secondary inducible pluripotent stem (iPS) system.
  • Manipulated mTOR activity via Tsc2 shRNA knockdown and rapamycin treatment.

Main Results:

  • Somatic cell reprogramming was completely inhibited in Tsc2(-/-) cells with hyperactivated mTOR.
  • Elevating mTOR activity or completely blocking it with rapamycin significantly impaired reprogramming efficiency in the iPS system.
  • Optimal iPS induction efficiency was achieved only with finely tuned mTOR activity.

Conclusions:

  • Elaborate regulation of mTOR activity is essential for successful somatic cell reprogramming into iPS cells.
  • Both hyperactivation and complete inhibition of mTOR negatively impact the reprogramming process.
  • Precise control over mTOR signaling is a critical determinant for generating induced pluripotent stem cells.

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