Metastable Pluripotent States in NOD-Mouse-Derived ESCs

被引：271

作者：

Hanna, Jacob ^{[1
]}

Markoulaki, Styliani ^{[1
]}

Mitalipova, Maisam ^{[1
]}

Cheng, Albert W. ^{[1
,2
]}

Cassady, John P. ^{[1
,3
]}

Staerk, Judith ^{[1
]}

Carey, Bryce W. ^{[1
,3
]}

Lengner, Christopher J. ^{[1
]}

Foreman, Ruth ^{[1
,3
]}

Love, Jennifer ^{[1
]}

Gao, Qing ^{[1
]}

Kim, Jongpil ^{[1
]}

Jaenisch, Rudolf ^{[1
,3
]}

机构：

[1] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

[2] MIT, Computat & Syst Biol Program, Cambridge, MA 02142 USA

[3] MIT, Dept Biol, Cambridge, MA 02142 USA

来源：

CELL STEM CELL | 2009年 / 4卷 / 06期

关键词：

EMBRYONIC STEM-CELLS; NUCLEAR TRANSFER; RAT BLASTOCYSTS; GROUND-STATE; SELF-RENEWAL; FIBROBLASTS; INDUCTION; DERIVATION; CIRCUITRY; LINES;

D O I：

10.1016/j.stem.2009.04.015

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Embryonic stem cells (ESCs) are isolated from the inner cell mass (ICM) of blastocysts, whereas epiblast stem cells (EpiSCs) are derived from the postimplantation epiblast and display a restricted developmental potential. Here we characterize pluripotent states in the nonobese diabetic (NOD) mouse strain, which prior to this study was considered "nonpermissive" for ESC derivation. We find that NOD stem cells can be stabilized by providing constitutive expression of Klf4 or c-Myc or small molecules that can replace these factors during in vitro reprogramming. The NOD ESCs and iPSCs appear to be "metastable," as they acquire an alternative EpiSC-like identity after removal of the exogenous factors, while their reintroduction converts the cells back to ICM-like pluripotency. Our findings suggest that stem cells from different genetic backgrounds can assume distinct states of pluripotency in vitro, the stability of which is regulated by endogenous genetic determinants and can be modified by exogenous factors.

引用

页码：513 / 524

页数：12

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