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Ground-State Conditions Promote Robust Prdm14 Reactivation and Maintain an Active Dlk1-Dio3 Region during Reprogramming

  • Habib, Omer (Department of Stem Cell Biology, School of Medicine, Konkuk University) ;
  • Habib, Gizem (Department of Stem Cell Biology, School of Medicine, Konkuk University) ;
  • Moon, Sung-Hwan (Department of Stem Cell Biology, School of Medicine, Konkuk University) ;
  • Hong, Ki-Sung (Stem Cell Research Laboratory, CHA Stem Cell Institute, CHA University) ;
  • Do, Jeong Tae (Laboratory of Stem Cell and Developmental Biology Department of Animal Biotechnology, College of Animal Bioscience and Technology, Konkuk University) ;
  • Choi, Youngsok (Department of Biomedical Science, CHA University) ;
  • Chang, Sung Woon (Department of Obstetrics and Gynecology, Bundang CHA General Hospital) ;
  • Chung, Hyung-Min (Department of Stem Cell Biology, School of Medicine, Konkuk University)
  • Received : 2013.07.23
  • Accepted : 2013.11.15
  • Published : 2014.01.31

Abstract

Induced pluripotent stem cells (iPSCs) are capable of unlimited self-renewal and can give rise to all three germ layers, thereby providing a new platform with which to study mammalian development and epigenetic reprogramming. However, iPSC generation may result in subtle epigenetic variations, such as the aberrant methylation of the Dlk1-Dio3 locus, among the clones, and this heterogeneity constitutes a major drawback to harnessing the full potential of iPSCs. Vitamin C has recently emerged as a safeguard to ensure the normal imprinting of the Dlk1-Dio3 locus during reprogramming. Here, we show that vitamin C exerts its effect in a manner that is independent of the reprogramming kinetics. Moreover, we demonstrate that reprogramming cells under 2i conditions leads to the early upregulation of Prdm14, which in turn results in a highly homogeneous population of authentic pluripotent colonies and prevents the abnormal silencing of the Dlk1-Dio3 locus.

Keywords

References

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