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

Abstract

Fork-head transcription factors are required for the maintenance of somatic stem cells. FOXO1 is now found to directly control the expression of pluripotency regulators in human embryonic stem cells, with a FOXO1 orthologue performing a similar function in mouse embryonic stem cells. Pluripotency of embryonic stem cells (ESCs) is defined by their ability to differentiate into three germ layers and derivative cell types1,2,3 and is established by an interactive network of proteins including OCT4 (also known as POU5F1; ref. 4), NANOG (refs 5, 6), SOX2 (ref. 7) 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 cells8,9,10,11,12,13; 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.

Cite this article

Zhang, X., Yalcin, S., Lee, DF. et al. FOXO1 is an essential regulator of pluripotency in human embryonic stem cells. Nat Cell Biol 13, 1092–1099 (2011). https://doi.org/10.1038/ncb2293

View full text

>> Full Text:   FOXO1 is an essential regulator of pluripotency in human embryonic stem cells