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Conversion of mouse epiblast stem cells to an earlier pluripotency state by small molecules.


ABSTRACT: Epiblast stem cells (EpiSCs) are pluripotent cells derived from post-implantation late epiblasts in vitro. EpiSCs are incapable of contributing to chimerism, indicating that EpiSCs are less pluripotent and represent a later developmental pluripotency state compared with inner cell mass stage murine embryonic stem cells (mESCs). Using a chemical approach, we found that blockage of the TGF? pathway or inhibition of histone demethylase LSD1 with small molecule inhibitors induced dramatic morphological changes in EpiSCs toward mESC phenotypes with simultaneous activation of inner cell mass-specific gene expression. However, full conversion of EpiSCs to the mESC-like state with chimerism competence could be readily generated only with the combination of LSD1, ALK5, MEK, FGFR, and GSK3 inhibitors. Our results demonstrate that appropriate synergy of epigenetic and signaling modulations could convert cells at the later developmental pluripotency state to the earlier mESC-like pluripotency state, providing new insights into pluripotency regulation.

SUBMITTER: Zhou H 

PROVIDER: S-EPMC2943300 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Conversion of mouse epiblast stem cells to an earlier pluripotency state by small molecules.

Zhou Hongyan H   Li Wenlin W   Zhu Saiyong S   Joo Jin Young JY   Do Jeong Tae JT   Xiong Wen W   Kim Jeong Beom JB   Zhang Kang K   Schöler Hans R HR   Ding Sheng S  

The Journal of biological chemistry 20100812 39


Epiblast stem cells (EpiSCs) are pluripotent cells derived from post-implantation late epiblasts in vitro. EpiSCs are incapable of contributing to chimerism, indicating that EpiSCs are less pluripotent and represent a later developmental pluripotency state compared with inner cell mass stage murine embryonic stem cells (mESCs). Using a chemical approach, we found that blockage of the TGFβ pathway or inhibition of histone demethylase LSD1 with small molecule inhibitors induced dramatic morphologi  ...[more]

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