Xist Repression Shows Time‐Dependent Effects on the Reprogramming of Female Somatic Cells to Induced Pluripotent Stem Cells. (October 2014)

• Record Type: Journal Article
• Authors: Chen, Qi; Gao, Shuai; He, Wenteng; Kou, Xiaochen; Zhao, Yanhong; Wang, Hong; Gao, Shaorong
• Is Part Of: Stem cells. Volume 32:Number 10(2014:Oct.)
• Page Start: 2642
• Page End: 2656
• Publication Date: 2014-10
• Subjects: Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.1775
• Languages: English
• ISSNs: 1066-5099

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>Although the reactivation of silenced X chromosomes has been observed as part of the process of reprogramming female somatic cells into induced pluripotent stem cells (iPSCs), it remains unknown whether repression of the X‐inactive specific transcript (<italic>Xist</italic>) can greatly enhance female iPSC induction similar to that observed in somatic cell nuclear transfer studies. In this study, we discovered that the repression of <italic>Xist</italic> plays opposite roles in the early and late phases of female iPSCs induction. Our results demonstrate that the downregulation of <italic>Xist</italic> by an isopropyl β‐<sc>d</sc>‐1‐thiogalactopyranoside (IPTG)‐inducible short hairpin RNA (shRNA) system can greatly impair the mesenchymal‐to‐epithelial transition (MET) in the early phase of iPSC induction but can significantly promote the transition of pre‐iPSCs to iPSCs in the late phase. Furthermore, we demonstrate that although the knockdown of <italic>Xist</italic> did not affect the H3K27me3 modification on the X chromosome, macroH2A was released from the inactivated X chromosome (Xi). This enables the X chromosome silencing to be a reversible event. Moreover, we demonstrate that the supplementation of vitamin C (Vc) can augment and stabilize the reversible X chromosome by preventing the relocalization of macroH2A to the Xi. Therefore, our study reveals an opposite role of <italic>Xist</italic> repression in the early and late stages of reprogramming female somatic cells to pluripotency and demonstrates that the release of macroH2A by <italic>Xist</italic> repression enables the transition from pre‐iPSCs to iPSCs. S<sc>tem</sc> C<sc>ells</sc><italic>2014;32:2642–2656</italic></p> </abstract>