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

^*Corresponding author for this work

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

14 Scopus citations

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 (US)
Pages (from-to)	713-725
Number of pages	13
Journal	STEM CELLS
Volume	33
Issue number	3
DOIs	https://doi.org/10.1002/stem.1893
State	Published - Mar 1 2015
Externally published	Yes

Keywords

Embryonic stem cells
MAPK
Myc
PI3K
Pluripotency

ASJC Scopus subject areas

General Medicine

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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., Carlos Izpisua Belmonte, J., & Okuda, A. (2015). Functional compensation between Myc and PI3K signaling supports self-renewal of embryonic stem cells. STEM CELLS, 33(3), 713-725. https://doi.org/10.1002/stem.1893

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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 = "Embryonic stem cells, MAPK, Myc, PI3K, Pluripotency",

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 {Carlos Izpisua Belmonte}, Juan and Akihiko Okuda",

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doi = "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, Carlos Izpisua Belmonte, J & Okuda, A 2015, 'Functional compensation between Myc and PI3K signaling supports self-renewal of embryonic stem cells', STEM CELLS, vol. 33, no. 3, pp. 713-725. https://doi.org/10.1002/stem.1893

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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 - Carlos Izpisua Belmonte, Juan

AU - Okuda, Akihiko

PY - 2015/3/1

Y1 - 2015/3/1

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.

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

Abstract

Keywords

ASJC Scopus subject areas

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