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; 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.
| Original language | English |
|---|---|
| Pages (from-to) | 1092-1101 |
| Number of pages | 10 |
| Journal | Nature Cell Biology |
| Volume | 13 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2011 Sep 1 |
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All Science Journal Classification (ASJC) codes
- Cell Biology
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FOXO1 is an essential regulator of pluripotency in human embryonic stem cells. / Zhang, Xin; Yalcin, Safak; Lee, Dung Fang; Yeh, Tsung Yin J.; Lee, Seung Min; Su, Jie; Mungamuri, Sathish Kumar; Rimmelé, Pauline; Kennedy, Marion; Sellers, Rani; Landthaler, Markus; Tuschl, Thomas; Chi, Nai Wen; Lemischka, Ihor; Keller, Gordon; Ghaffari, Saghi.
In: Nature Cell Biology, Vol. 13, No. 9, 01.09.2011, p. 1092-1101.Research output: Contribution to journal › Article
TY - JOUR
T1 - FOXO1 is an essential regulator of pluripotency in human embryonic stem cells
AU - Zhang, Xin
AU - Yalcin, Safak
AU - Lee, Dung Fang
AU - Yeh, Tsung Yin J.
AU - Lee, Seung Min
AU - Su, Jie
AU - Mungamuri, Sathish Kumar
AU - Rimmelé, Pauline
AU - Kennedy, Marion
AU - Sellers, Rani
AU - Landthaler, Markus
AU - Tuschl, Thomas
AU - Chi, Nai Wen
AU - Lemischka, Ihor
AU - Keller, Gordon
AU - Ghaffari, Saghi
PY - 2011/9/1
Y1 - 2011/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=80052490840&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80052490840&partnerID=8YFLogxK
U2 - 10.1038/ncb2293
DO - 10.1038/ncb2293
M3 - Article
C2 - 21804543
AN - SCOPUS:80052490840
VL - 13
SP - 1092
EP - 1101
JO - Nature Cell Biology
JF - Nature Cell Biology
SN - 1465-7392
IS - 9
ER -