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J. Biol. Chem., Vol. 282, Issue 8, 5842-5852, February 23, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/8/5842    most recent M610464200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Qin, H. Articles by Deng, H. Search for Related Content PubMed PubMed Citation Articles by Qin, H. Articles by Deng, H. Social Bookmarking                      What's this?

Regulation of Apoptosis and Differentiation by p53 in Human Embryonic Stem Cells^*

Han Qin, Tianxin Yu, Tingting Qing, Yanxia Liu, Yang Zhao, Jun Cai, Jian Li, Zhihua Song, Xiuxia Qu, Peng Zhou, Jiong Wu^¶, Mingxiao Ding¹, and Hongkui Deng²

From the Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, College of Life Sciences, Peking University, Yiheyuan Road 5, Beijing 100871, China, the Laboratory of Chemical Genomics, Shenzhen Graduate School of Peking University, The University Town, Shenzhen 518055, China, and ^¶Cell Signaling Technology, Inc., Danvers, Massachusetts 01923

The essentially infinite expansion potential and pluripotency of human embryonic stem cells (hESCs) makes them attractive for cell-based therapeutics. In contrast to mouse embryonic stem cells (mESCs), hESCs normally undergo high rates of spontaneous apoptosis and differentiation, making them difficult to maintain in culture. Here we demonstrate that p53 protein accumulates in apoptotic hESCs induced by agents that damage DNA. However, despite the accumulation of p53, it nevertheless fails to activate the transcription of its target genes. This inability of p53 to activate its target genes has not been observed in other cell types, including mESCs. We further demonstrate that p53 induces apoptosis of hESCs through a mitochondrial pathway. Reducing p53 expression in hESCs in turn reduces both DNA damage-induced apoptosis as well as spontaneous apoptosis. Reducing p53 expression also reduces spontaneous differentiation and slows the differentiation rate of hESCs. Our studies reveal the important roles of p53 as a critical mediator of human embryonic stem cells survival and differentiation.

Received for publication, November 9, 2006 , and in revised form, December 18, 2006.

^* This work was supported by the Ministry of Science and Technology (Grant 2001CB510106), the Science and Technology Plan of Beijing Municipal Government (Grant H020220050290), the National Nature Science Foundation of China for Creative Research Groups (Grant 30421004), and the Bill and Melinda Gates Foundation (Grant 37871) (to H. D.). The authors declare competing financial interests. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental "Experimental Procedures" and Figs. S1-S3.

¹ To whom correspondence may be addressed. Tel./Fax: 86-10-6275-6369; E-mail: dingmx01{at}pku.edu.cn.

² To whom correspondence may be addressed. Tel./Fax: 86-10-6275-6954; E-mail: address: hongkui_deng{at}pku.edu.cn.

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