Functional compensation between Myc and PI3K signaling supports self-renewal of embryonic stem cells.
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.
Division of Developmental Biology, Research Center for Genomic Medicine, Saitama Medical University, Yamane, Hidaka, Saitama, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Kawaguchi, Saitama, Japan; Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California, USA.
Tomoaki
T
Hishida
Yutaka
Y
Nakachi
Yosuke
Y
Mizuno
Miyuki
M
Katano
Yasushi
Y
Okazaki
Masatsugu
M
Ema
Satoru
S
Takahashi
Masataka
M
Hirasaki
Ayumu
A
Suzuki
Atsushi
A
Ueda
Masazumi
M
Nishimoto
Yuriko
Y
Hishida-Nozaki
Eric
E
Vazquez-Ferrer
Ignacio
I
Sancho-Martinez
Juan Carlos
JC
Izpisua Belmonte
Akihiko
A
Okuda
D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D020928:Mitogen-Activated Protein Kinases; D051267:NF-E2-Related Factor 2; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D016271:Proto-Oncogene Proteins c-myc; C489428:Myc protein, mouse; C495636:Nfe2l2 protein, mouse; C068422:Max protein, mouse
Embryonic stem cells; MAPK; Myc; PI3K; Pluripotency