Dppa3 expression is critical for generation of fully reprogrammed iPS cells and maintenance of Dlk1-Dio3 imprinting

DOI PDF Web Site PubMed 研究データあり 被引用文献2件 参考文献44件 オープンアクセス

書誌事項

公開日
2015-01-23
資源種別
journal article
権利情報
  • https://creativecommons.org/licenses/by/4.0
  • https://creativecommons.org/licenses/by/4.0
DOI
  • 10.1038/ncomms7008
公開者
Springer Science and Business Media LLC

説明

<jats:title>Abstract</jats:title><jats:p>Reprogramming of mouse somatic cells into induced pluripotent stem cells (iPSCs) often generates partially reprogrammed iPSCs (pre-iPSCs), low-grade chimera forming iPSCs (lg-iPSCs) and fully reprogrammed, high-grade chimera production competent iPSCs (hg-iPSCs). Lg-iPSC transcriptome analysis revealed misregulated <jats:italic>Dlk1-Dio3</jats:italic> cluster gene expression and subsequently the imprinting defect at the <jats:italic>Dlk1-Dio3</jats:italic> locus. Here, we show that germ-cell marker <jats:italic>Dppa3</jats:italic> is present only in lg-iPSCs and hg-iPSCs, and that induction with exogenous <jats:italic>Dppa3</jats:italic> enhances reprogramming kinetics, generating all hg-iPSCs, similar to vitamin C (Vc). Conversely, <jats:italic>Dppa3</jats:italic>-null fibroblasts show reprogramming block at pre-iPSCs state and <jats:italic>Dlk1-Dio3</jats:italic> imprinting defect. At the molecular level, we show that Dppa3 is associated with <jats:italic>Dlk1-Dio3</jats:italic> locus and identify that Dppa3 maintains imprinting by antagonizing Dnmt3a binding. Our results further show molecular parallels between Dppa3 and Vc in <jats:italic>Dlk1-Dio3</jats:italic> imprinting maintenance and suggest that early activation of <jats:italic>Dppa3</jats:italic> is one of the cascades through which Vc facilitates the generation of fully reprogrammed iPSCs.</jats:p>

収録刊行物

  • Nature Communications

    Nature Communications 6 (1), 6008-, 2015-01-23

    Springer Science and Business Media LLC

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