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Protein Kinase A Signaling Is Inhibitory for Reprogramming into Pluripotent Stem Cells

Jong Soo Kim1, Yean Ju Hong1, Hyun Woo Choi1

  • 1Department of Animal Biotechnology, College of Animal Bioscience and Technology, Konkuk University , Seoul, Republic of Korea.

Stem Cells and Development
|January 6, 2016
PubMed

Insights

Small molecules like 8-Bromoadenosine 3

Area of Science:

  • Stem cell biology
  • Molecular biology
  • Cellular reprogramming

Background:

  • Induced pluripotent stem cells (iPSCs) are generated by reprogramming somatic cells using transcription factors.
  • Low efficiency and slow kinetics are major hurdles in iPSC generation.
  • Small molecules are being investigated to improve reprogramming efficiency.

Purpose of the Study:

  • To investigate the effect of small molecules on cellular reprogramming efficiency.
  • To identify factors that enhance the generation of induced pluripotent stem cells.

Main Methods:

  • Treatment of reprogrammable mouse fibroblasts with 8-Bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP).
  • Culture in serum replacement (SR) medium with doxycycline induction.
  • Inhibition of protein kinase A (PKA) activity.

Main Results:

  • 8-Br-cAMP, a cyclic adenosine monophosphate (cAMP) analog, significantly improved reprogramming efficiency in SR medium.
  • 8-Br-cAMP did not affect reprogramming under mouse embryonic stem cell culture conditions.
  • Inhibition of PKA in SR medium enhanced reprogramming efficiency, suggesting PKA acts as a barrier.

Conclusions:

  • PKA signaling may impede the reprogramming of somatic cells into pluripotent stem cells.
  • Targeting PKA signaling could be a strategy to enhance iPSC generation.
  • 8-Br-cAMP shows potential for improving reprogramming protocols.

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