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

Autor: Markus Landthaler, Saghi Ghaffari, Nai Wen Chi, Jie Su, Gordon Keller, Xin Zhang, Rani S. Sellers, Pauline Rimmele, Sathish Kumar Mungamuri, Marion Kennedy, Thomas Tuschl, Tsung Yin J. Yeh, Ihor R. Lemischka, Safak Yalcin, Dung Fang Lee, Seung Min Lee
Rok vydání: 2011
Předmět:
Pluripotent Stem Cells
Homeobox protein NANOG
endocrine system
Rex1
Blotting
Western
Molecular Sequence Data
Gene Expression
Apoptosis
Regulatory Sequences
Nucleic Acid
Biology
Article
Cell Line
SOX2
Animals
Humans
Phosphorylation
Induced pluripotent stem cell
Cell potency
Embryonic Stem Cells
reproductive and urinary physiology
Cell Proliferation
Homeodomain Proteins
Base Sequence
Forkhead Box Protein O1
Reverse Transcriptase Polymerase Chain Reaction
Gene Expression Profiling
SOXB1 Transcription Factors
Nanog Homeobox Protein
Forkhead Transcription Factors
Cell Biology
Embryonic stem cell
Cell biology
HEK293 Cells
Doxycycline
embryonic structures
RNA Interference
biological phenomena
cell phenomena
and immunity
Reactive Oxygen Species
Octamer Transcription Factor-3
Proto-Oncogene Proteins c-akt
Reprogramming
hormones
hormone substitutes
and hormone antagonists
Protein Binding
Zdroj: Nature Cell Biology. 13:1092-1099
ISSN: 1476-4679
1465-7392
Popis: Pluripotency of embryonic stem cells (ESCs) is defined by their ability to differentiate into three germ layers and derivative cell types1-3 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 cells8-13; 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.
Databáze: OpenAIRE
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