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FOXO1 is an essential regulator of pluripotency in human embryonic stem cells

Item Type:Article
Title:FOXO1 is an essential regulator of pluripotency in human embryonic stem cells
Creators Name:Zhang, X. and Yalcin, S. and Lee, D.F. and Yeh, T.Y. and Lee, S.M. and Su, J. and Mungamuri, S.K. and Rimmele, P. and Kennedy, M. and Sellers, R. and Landthaler, M. and Tuschl, T. and Chi, N.W. and Lemischka, I. and Keller, G. and Ghaffari, S.
Abstract: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), NANOG, SOX2 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.
Keywords:Apoptosis, Base Sequence, Western Blotting, Cell Line, Cell Proliferation, Doxycycline, Embryonic Stem Cells, Forkhead Transcription Factors, Gene Expression, Gene Expression Profiling, HEK293 Cells, Homeodomain Proteins, Molecular Sequence Data, Octamer Transcription Factor-3, Phosphorylation, Pluripotent Stem Cells, Protein Binding, Proto-Oncogene Proteins c-akt, RNA Interference, Reactive Oxygen Species, Nucleic Acid Regulatory Sequences, Reverse Transcriptase Polymerase Chain Reaction, SOXB1 Transcription Factors
Source:Nature Cell Biology
Publisher:Nature Publishing Group
Page Range:1092-1099
Date:31 July 2011
Official Publication:https://doi.org/10.1038/ncb2293
PubMed:View item in PubMed

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