FOXO1 is an essential regulator of pluripotency in human embryonic stem cells.
FOXO1 is an essential regulator of pluripotency in human embryonic stem cells.
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DOI:
10.1038/ncb2293
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发表时间:
2011-07-31
影响因子:
21.3
通讯作者:
中科院分区:
文献类型:
--
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Pluripotency of embryonic stem cells (ESCs) is defined by their ability to differentiate into three germ layers and derivative cell types and is established by an interactive network of proteins including OCT4 (also known as POU5F1; ref.), NANOG (refs), SOX2 (ref.) and their binding partners. The forkhead box O (FoxO) transcription factors are evolutionarily conserved regulators of longevity and stress response whose function is inhibited by AKT protein kinase. FoxO proteins are required for the maintenance of somatic and cancer stem cells; however, their function in ESCs is unknown. We show that FOXO1 is essential for the maintenance of human ESC pluripotency, and that an orthologue of FOXO1 (Foxo1) exerts a similar function in mouse ESCs. This function is probably mediated through direct control by FOXO1 of OCT4 and SOX2 gene expression through occupation and activation of their respective promoters. Finally, AKT is not the predominant regulator of FOXO1 in human ESCs. Together these results indicate that FOXO1 is a component of the circuitry of human ESC pluripotency. These findings have critical implications for stem cell biology, development, longevity and reprogramming, with potentially important ramifications for therapy.
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影响因子:
64.5
作者:
Brunet, A;Bonni, A;Greenberg, ME
通讯作者:
Greenberg, ME
DOI:
10.1073/pnas.0406789102
发表时间:
2005-02-01
影响因子:
11.1
作者:
Huang, H;Regan, KM;Tindall, DJ
通讯作者:
Tindall, DJ
影响因子:
21.3
作者:
Jiang, Jianming;Chan, Yun-Shen;Ng, Huck-Hui
通讯作者:
Ng, Huck-Hui
影响因子:
14.8
作者:
Dansen, Tobias B.;Smits, Lydia M. M.;Burgering, Boudewijn M. T.
通讯作者:
Burgering, Boudewijn M. T.
影响因子:
23.9
作者:
Lee, Jae Y.;Nakada, Daisuke;Yilmaz, Omer H.;Tothova, Zuzana;Joseph, Nancy M.;Lim, Megan S.;Gilliland, D. Gary;Morrison, Sean J.
通讯作者:
Morrison, Sean J.