Functional compensation between Myc and PI3K signaling supports self-renewal of embryonic stem cells

Tomoaki Hishida, Yutaka Nakachi, Yosuke Mizuno, Miyuki Katano, Yasushi Okazaki, Masatsugu Ema, Satoru Takahashi, Masataka Hirasaki, Ayumu Suzuki, Atsushi Ueda, Masazumi Nishimoto, Yuriko Hishida-Nozaki, Eric Vazquez-Ferrer, Ignacio Sancho-Martinez, Juan Carlos Izpisua Belmonte*, Akihiko Okuda

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


c-Myc and phosphatidylinositol 3-OH kinase (PI3K) both participate in diverse cellular processes, including cell cycle control and tumorigenic transformation. They also contribute to preserving embryonic stem cell (ESC) characteristics. However, in spite of the vast knowledge, the molecular relationship between c-Myc and PI3K in ESCs is not known. Herein, we demonstrate that c-Myc and PI3K function cooperatively but independently to support ESC self-renewal when murine ESCs are cultured under conventional culture condition. Interestingly, culture of ESCs in 2i-condition including a GSK3β and MEK inhibitor renders both PI3K and Myc signaling dispensable for the maintenance of pluripotent properties. These results suggest that the requirement for an oncogenic proliferation-dependent mechanism sustained by Myc and PI3K is context dependent and that the 2i-condition liberates ESCs from the dependence of this mechanism. Stem Cells 2015;33:713-725

Original languageEnglish (US)
Pages (from-to)713-725
Number of pages13
JournalStem Cells
Issue number3
StatePublished - Mar 1 2015


  • Embryonic stem cells
  • MAPK
  • Myc
  • PI3K
  • Pluripotency

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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