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

doi:10.1002/stem.1893

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

Centre for Stem Cells & Regenerative Medicine

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

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.

Original language	English
Pages (from-to)	713-25
Number of pages	13
Journal	Stem cells (Dayton, Ohio)
Volume	33
Issue number	3
Early online date	17 Feb 2015
DOIs	https://doi.org/10.1002/stem.1893
Publication status	Published - Mar 2015

Keywords

Animals
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Cell Differentiation
Cell Proliferation
Embryonic Stem Cells
MAP Kinase Signaling System
Mice
Mitogen-Activated Protein Kinases
NF-E2-Related Factor 2
Phosphatidylinositol 3-Kinases
Pluripotent Stem Cells
Proto-Oncogene Proteins c-myc

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/stem.1893

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Hishida, T., Nakachi, Y., Mizuno, Y., Katano, M., Okazaki, Y., Ema, M., Takahashi, S., Hirasaki, M., Suzuki, A., Ueda, A., Nishimoto, M., Hishida-Nozaki, Y., Vazquez-Ferrer, E., Sancho-Martinez, I., Izpisua Belmonte, J. C., & Okuda, A. (2015). Functional compensation between Myc and PI3K signaling supports self-renewal of embryonic stem cells. Stem cells (Dayton, Ohio), 33(3), 713-25. https://doi.org/10.1002/stem.1893

@article{c170d760650e4e88b66ee7db10701e35,

title = "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.",

keywords = "Animals, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Cell Differentiation, Cell Proliferation, Embryonic Stem Cells, MAP Kinase Signaling System, Mice, Mitogen-Activated Protein Kinases, NF-E2-Related Factor 2, Phosphatidylinositol 3-Kinases, Pluripotent Stem Cells, Proto-Oncogene Proteins c-myc",

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

note = "{\textcopyright} 2014 AlphaMed Press.",

year = "2015",

month = mar,

doi = "10.1002/stem.1893",

language = "English",

volume = "33",

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Hishida, T, Nakachi, Y, Mizuno, Y, Katano, M, Okazaki, Y, Ema, M, Takahashi, S, Hirasaki, M, Suzuki, A, Ueda, A, Nishimoto, M, Hishida-Nozaki, Y, Vazquez-Ferrer, E, Sancho-Martinez, I, Izpisua Belmonte, JC & Okuda, A 2015, 'Functional compensation between Myc and PI3K signaling supports self-renewal of embryonic stem cells', Stem cells (Dayton, Ohio), vol. 33, no. 3, pp. 713-25. https://doi.org/10.1002/stem.1893

TY - JOUR

T1 - Functional compensation between Myc and PI3K signaling supports self-renewal of embryonic stem cells

AU - Hishida, Tomoaki

AU - Nakachi, Yutaka

AU - Mizuno, Yosuke

AU - Katano, Miyuki

AU - Okazaki, Yasushi

AU - Ema, Masatsugu

AU - Takahashi, Satoru

AU - Hirasaki, Masataka

AU - Suzuki, Ayumu

AU - Ueda, Atsushi

AU - Nishimoto, Masazumi

AU - Hishida-Nozaki, Yuriko

AU - Vazquez-Ferrer, Eric

AU - Sancho-Martinez, Ignacio

AU - Izpisua Belmonte, Juan Carlos

AU - Okuda, Akihiko

PY - 2015/3

Y1 - 2015/3

N2 - 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.

AB - 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.

KW - Animals

KW - Basic Helix-Loop-Helix Leucine Zipper Transcription Factors

KW - Cell Differentiation

KW - Cell Proliferation

KW - Embryonic Stem Cells

KW - MAP Kinase Signaling System

KW - Mice

KW - Mitogen-Activated Protein Kinases

KW - NF-E2-Related Factor 2

KW - Phosphatidylinositol 3-Kinases

KW - Pluripotent Stem Cells

KW - Proto-Oncogene Proteins c-myc

U2 - 10.1002/stem.1893

DO - 10.1002/stem.1893

M3 - Article

C2 - 25385436

SN - 1066-5099

VL - 33

SP - 713

EP - 725

JO - Stem cells (Dayton, Ohio)

JF - Stem cells (Dayton, Ohio)

IS - 3

ER -

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

Abstract

Keywords

UN SDGs

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