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microRNA-29b is a novel mediator of Sox2 function in the regulation of somatic cell reprogramming

Xudong Guo1, Qidong Liu, Guiying Wang

  • 1Clinical and Translational Research Center of Shanghai First Maternity & Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, China.

Cell Research
|December 26, 2012
PubMed

Insights

Sox2 regulates microRNA-29b (miR-29b) during induced pluripotent stem cell (iPSC) generation. This miR-29b then targets DNA methyltransferases (DNMTs), impacting DNA methylation and reprogramming efficiency.

Area of Science:

  • Stem cell biology
  • Epigenetics
  • Molecular mechanisms of reprogramming

Background:

  • Fibroblast reprogramming into induced pluripotent stem cells (iPSCs) is crucial for regenerative medicine.
  • The precise molecular mechanisms governing this cellular reprogramming are not fully elucidated.

Purpose of the Study:

  • To investigate the role of Sox2 and microRNA-29b (miR-29b) in the reprogramming process.
  • To elucidate the downstream targets and signaling pathways regulated by miR-29b during iPSC generation.

Main Methods:

  • Analysis of Sox2's direct regulation of miR-29b expression.
  • Investigating miR-29b's requirement for OSKM- and OSK-mediated reprogramming.
  • Identifying in vivo targets of miR-29b using mechanistic studies.
  • Assessing the impact of miR-29b and DNA methyltransferases (DNMTs) on DNA methylation events like MET and Dlk1-Dio3 transcription.

Main Results:

  • Sox2 directly regulates endogenous miR-29b expression during iPSC generation.
  • miR-29b is essential for OSKM- and OSK-induced reprogramming.
  • Dnmt3a and Dnmt3b were identified as in vivo targets of miR-29b.
  • miR-29b expression is inversely correlated with Dnmt3a and Dnmt3b levels during reprogramming.
  • Overexpression of Dnmt3a or Dnmt3b can block the reprogramming effects of miR-29b.
  • The miR-29b-DNMT signaling pathway regulates DNA methylation events, including MET and Dlk1-Dio3 transcription.

Conclusions:

  • miR-29b acts as a novel mediator regulated by the reprogramming factor Sox2.
  • Sox2 initiates a miR-29b-DNMT signaling axis that controls DNA methylation-related events during reprogramming.
  • This study reveals a multistep mechanism essential for efficient iPSC generation.

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