mTOR supports long-term self-renewal and suppresses mesoderm and endoderm activities of human embryonic stem cells

Jiaxi Zhou, Pei Su, Lu Wang, Joanna Chen, Maike Zimmermann, Olga Genbacev, Olubunmi Afonja, Mary C Horne, Tetsuya Tanaka, Enkui Duan, Susan J. Fisher, Jiayu Liao, Jie Chen, Fei Wang

Research output: Contribution to journalArticle

138 Scopus citations

Abstract

Despite the recent identification of the transcriptional regulatory circuitry involving SOX2, NANOG, and OCT-4, the intracellular signaling networks that control pluripotency of human embryonic stem cells (hESCs) remain largely undefined. Here, we demonstrate an essential role for the serine/threonine protein kinase mammalian target of rapamycin (mTOR) in regulating hESC long-term undifferentiated growth. Inhibition of mTOR impairs pluripotency, prevents cell proliferation, and enhances mesoderm and endoderm activities in hESCs. At the molecular level, mTOR integrates signals from extrinsic pluripotency-supporting factors and represses the transcriptional activities of a subset of developmental and growth-inhibitory genes, as revealed by genome-wide microarray analyses. Repression of the developmental genes by mTOR is necessary for the maintenance of hESC pluripotency. These results uncover a novel signaling mechanism by which mTOR controls fate decisions in hESCs. Our findings may contribute to effective strategies for tissue repair and regeneration.

Original languageEnglish (US)
Pages (from-to)7840-7845
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number19
DOIs
StatePublished - May 12 2009
Externally publishedYes

Keywords

  • Differentiation
  • Long-term undifferentiated growth
  • OCT-4
  • Pluripotency

ASJC Scopus subject areas

  • General

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  • Cite this

    Zhou, J., Su, P., Wang, L., Chen, J., Zimmermann, M., Genbacev, O., Afonja, O., Horne, M. C., Tanaka, T., Duan, E., Fisher, S. J., Liao, J., Chen, J., & Wang, F. (2009). mTOR supports long-term self-renewal and suppresses mesoderm and endoderm activities of human embryonic stem cells. Proceedings of the National Academy of Sciences of the United States of America, 106(19), 7840-7845. https://doi.org/10.1073/pnas.0901854106