Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs

被引：637

作者：

Hanna, Jacob ^{[1
]}

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

Saha, Krishanu ^{[1
]}

Kim, Jongpil ^{[1
]}

Lengner, Christopher J. ^{[1
]}

Soldner, Frank ^{[1
]}

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

Muffat, Julien ^{[1
]}

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

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：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 20期

关键词：

pluripotency; reprogramming; SELF-RENEWAL; GROUND-STATE; GERM-CELLS; PLURIPOTENCY; EPIBLAST; LINES; DERIVATION; INACTIVATION; FIBROBLASTS; BLASTOCYSTS;

D O I：

10.1073/pnas.1004584107

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Human and mouse embryonic stem cells (ESCs) are derived from blastocyst-stage embryos but have very different biological properties, and molecular analyses suggest that the pluripotent state of human ESCs isolated so far corresponds to that of mouse-derived epiblast stem cells (EpiSCs). Here we rewire the identity of conventional human ESCs into a more immature state that extensively shares defining features with pluripotent mouse ESCs. This was achieved by ectopic induction of Oct4, Klf4, and Klf2 factors combined with LIF and inhibitors of glycogen synthase kinase 3 beta (GSK3 beta) and mitogen-activated protein kinase (ERK1/2) pathway. Forskolin, a protein kinase A pathway agonist which can induce Klf4 and Klf2 expression, transiently substitutes for the requirement for ectopic transgene expression. In contrast to conventional human ESCs, these epigenetically converted cells have growth properties, an X-chromosome activation state (XaXa), a gene expression profile, and a signaling pathway dependence that are highly similar to those of mouse ESCs. Finally, the same growth conditions allow the derivation of human induced pluripotent stem (iPS) cells with similar properties as mouse iPS cells. The generation of validated "naive" human ESCs will allow the molecular dissection of a previously undefined pluripotent state in humans and may open up new opportunities for patient-specific, disease-relevant research.

引用

页码：9222 / 9227

页数：6

共 43 条

[11] Klf4 reverts developmentally programmed restriction of ground state pluripotency [J].