title: Ground-state conditions promote robust Prdm14 reactivation and maintain an active Dlk1-Dio3 region during reprogramming.
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.
authors.affiliation: Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul 143-701, Korea ; Stem Cell Research Laboratory, CHA Stem Cell Institute, CHA University, Seoul 135-907, Korea.
authors.forename: Omer
authors.initials: O
authors.lastname: Habib
authors.forename: Gizem
authors.initials: G
authors.lastname: Habib
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Moon
authors.forename: Ki-Sung
authors.initials: KS
authors.lastname: Hong
authors.forename: Jeong Tae
authors.initials: JT
authors.lastname: Do
authors.forename: Youngsok
authors.initials: Y
authors.lastname: Choi
authors.forename: Sung Woon
authors.initials: SW
authors.lastname: Chang
authors.forename: Hyung-Min
authors.initials: HM
authors.lastname: Chung
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D002135:Calcium-Binding Proteins; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D015870:Gene Expression; D056426:Genetic Loci; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism* / Q000637:transplantation; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D007453:Iodide Peroxidase / Q000235:genetics*; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D016601:RNA-Binding Proteins; D013724:Teratoma / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; C531066:Prdm14 protein, mouse; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C117274:iodothyronine deiodinase type III; D007453:Iodide Peroxidase; D001205:Ascorbic Acid