Ground-state conditions promote robust Prdm14 reactivation and maintain an active Dlk1-Dio3 region during reprogramming

Mol Cells. 2014 Jan;37(1):31-5. doi: 10.14348/molcells.2014.2212. Epub 2014 Jan 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ascorbic Acid / pharmacology
  • Calcium-Binding Proteins
  • Cells, Cultured
  • DNA-Binding Proteins
  • Gene Expression
  • Genetic Loci
  • Induced Pluripotent Stem Cells / metabolism*
  • Induced Pluripotent Stem Cells / transplantation
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Iodide Peroxidase / genetics*
  • Mice, Inbred NOD
  • Mice, SCID
  • Mice, Transgenic
  • RNA-Binding Proteins
  • Teratoma / pathology
  • Transcription Factors / metabolism*

Substances

  • Calcium-Binding Proteins
  • DNA-Binding Proteins
  • Dlk1 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Prdm14 protein, mouse
  • RNA-Binding Proteins
  • Transcription Factors
  • iodothyronine deiodinase type III
  • Iodide Peroxidase
  • Ascorbic Acid