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

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

Fingerprint

Endoderm
Mesoderm
Sirolimus
Developmental Genes
Protein-Serine-Threonine Kinases
Microarray Analysis
Growth
Regeneration
Maintenance
Cell Proliferation
Human Embryonic Stem Cells
Genome
Genes

Keywords

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

ASJC Scopus subject areas

  • General

Cite this

mTOR supports long-term self-renewal and suppresses mesoderm and endoderm activities of human embryonic stem cells. / Zhou, Jiaxi; Su, Pei; Wang, Lu; Chen, Joanna; Zimmermann, Maike; Genbacev, Olga; Afonja, Olubunmi; Horne, Mary C.; Tanaka, Tetsuya; Duan, Enkui; Fisher, Susan J.; Liao, Jiayu; Chen, Jie; Wang, Fei.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 19, 12.05.2009, p. 7840-7845.

Research output: Contribution to journalArticle

Zhou, J, Su, P, Wang, L, Chen, J, Zimmermann, M, Genbacev, O, Afonja, O, Horne, MC, Tanaka, T, Duan, E, Fisher, SJ, 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, vol. 106, no. 19, pp. 7840-7845. https://doi.org/10.1073/pnas.0901854106
Zhou, Jiaxi ; Su, Pei ; Wang, Lu ; Chen, Joanna ; Zimmermann, Maike ; Genbacev, Olga ; Afonja, Olubunmi ; Horne, Mary C. ; Tanaka, Tetsuya ; Duan, Enkui ; Fisher, Susan J. ; Liao, Jiayu ; Chen, Jie ; Wang, Fei. / mTOR supports long-term self-renewal and suppresses mesoderm and endoderm activities of human embryonic stem cells. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 19. pp. 7840-7845.
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