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Kim, Jeong Beom
Molecular Biomedicine Lab
Research Interests
  • Patient-specific stem cells, induced pluripotent stem (iPS) cells, direct conversion, 3D bio-printing, Regenerative medicine, Patient-specific drug screening

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Conversion of Mouse Epiblast Stem Cells to an Earlier Pluripotency State by Small Molecules

Cited 52 times inthomson ciCited 48 times inthomson ci
Title
Conversion of Mouse Epiblast Stem Cells to an Earlier Pluripotency State by Small Molecules
Author
Zhou, HongyanLi, WenlinZhu, SaiyongJoo, Jin YoungDo, Jeong TaeXiong, WenKim, Jeong BeomZhang, KangSchoeler, Hans R.Ding, Sheng
Keywords
Histone demethylase LSD1; In-vitro; Inner cell mass; Morphological changes; Murine embryonic stem cells; Pluripotency; Pluripotent; Post-implantation; Small molecule inhibitor; Small molecules
Issue Date
2010-09
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Citation
JOURNAL OF BIOLOGICAL CHEMISTRY, v.285, no.39, pp.29676 - 29680
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 beta 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.
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DOI
10.1074/jbc.C110.150599
ISSN
0021-9258
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BME_Journal Papers
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