Inhibition of transforming growth factor β (TGF-β) signaling can substitute for Oct4 protein in reprogramming and maintain pluripotency

Fangzhi Tan; Cheng Qian; Ke Tang; Saber Mohamed Abd-Allah; Naihe Jing

doi:10.1074/jbc.M114.609016

Inhibition of transforming growth factor β (TGF-β) signaling can substitute for Oct4 protein in reprogramming and maintain pluripotency

J Biol Chem. 2015 Feb 13;290(7):4500-11. doi: 10.1074/jbc.M114.609016. Epub 2014 Dec 29.

Authors

Fangzhi Tan¹, Cheng Qian¹, Ke Tang², Saber Mohamed Abd-Allah³, Naihe Jing⁴

Affiliations

¹ From the State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
² the Institute of Life Science, Nanchang University, Nanchang, Jiangxi 330031, China, and.
³ the Theriogenology Department, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef 62511, Egypt.
⁴ From the State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, [email protected].

Abstract

Mouse pluripotent stem cells (PSCs), such as ES cells and induced PSCs (iPSCs), are an excellent system to investigate the molecular and cellular mechanisms involved in early embryonic development. The signaling pathways orchestrated by leukemia inhibitor factor/STAT3, Wnt/β-catenin, and FGF/MEK/ERK play key roles in the generation of pluripotency. However, the function of TGF-β signaling in this process remains elusive. Here we show that inhibiting TGF-β signaling with its inhibitor SB431542 can substitute for Oct4 during reprogramming. Moreover, inhibiting TGF-β signaling can sustain the pluripotency of iPSCs and ES cells through modulating FGF/MEK/ERK signaling. Therefore, this study reveals a novel function of TGF-β signaling inhibition in the generation and maintenance of PSCs.

Keywords: ERK; ES Cell; Induced Pluripotent Stem Cell (iPSC); Oct4; Reprogramming; TGF-β.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Benzamides / pharmacology*
Blotting, Western
Cell Differentiation / drug effects
Cells, Cultured
Cellular Reprogramming / drug effects*
Dioxoles / pharmacology*
Embryo, Mammalian / cytology
Embryo, Mammalian / drug effects
Embryo, Mammalian / metabolism
Embryonic Stem Cells / cytology*
Embryonic Stem Cells / drug effects
Embryonic Stem Cells / metabolism
Extracellular Signal-Regulated MAP Kinases / genetics
Extracellular Signal-Regulated MAP Kinases / metabolism
Fibroblast Growth Factor 1 / genetics
Fibroblast Growth Factor 1 / metabolism
Fibroblasts / cytology
Fibroblasts / drug effects
Fibroblasts / metabolism
Fluorescent Antibody Technique
Induced Pluripotent Stem Cells / cytology*
Induced Pluripotent Stem Cells / drug effects
Induced Pluripotent Stem Cells / metabolism
MAP Kinase Kinase 1 / genetics
MAP Kinase Kinase 1 / metabolism
Mice
Mice, Inbred C57BL
Octamer Transcription Factor-3 / genetics
Octamer Transcription Factor-3 / metabolism*
RNA, Messenger / genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / drug effects
Transforming Growth Factor beta / antagonists & inhibitors*

Substances

4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide
Benzamides
Dioxoles
Octamer Transcription Factor-3
Pou5f1 protein, mouse
RNA, Messenger
Transforming Growth Factor beta
Fibroblast Growth Factor 1
Extracellular Signal-Regulated MAP Kinases
MAP Kinase Kinase 1