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

Abstract

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.

• Authors: 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
• Journal: Stem cells (Dayton, Ohio) (Stem Cells) Vol. 33 Issue 3 Pg. 713-25 (Mar 2015) ISSN: 1549-4918 [Electronic] England
• PMID: 25385436 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 AlphaMed Press.

Chemical References

• Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
• Myc protein, mouse
• NF-E2-Related Factor 2
• Nfe2l2 protein, mouse
• Phosphoinositide-3 Kinase Inhibitors
• Proto-Oncogene Proteins c-myc
• Max protein, mouse
• Mitogen-Activated Protein Kinases

Topics

• Animals
• Basic Helix-Loop-Helix Leucine Zipper Transcription Factors (biosynthesis, genetics)
• Cell Differentiation (physiology)
• Cell Proliferation (physiology)
• Embryonic Stem Cells (cytology, metabolism)
• MAP Kinase Signaling System
• Mice
• Mitogen-Activated Protein Kinases (antagonists & inhibitors, genetics, metabolism)
• NF-E2-Related Factor 2 (biosynthesis, genetics)
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Pluripotent Stem Cells (cytology, metabolism)
• Proto-Oncogene Proteins c-myc (genetics, metabolism)