A Small-Molecule Inhibitor of Tgf-β Signaling Replaces Sox2 in Reprogramming by Inducing Nanog

被引：639

作者：

Ichida, Justin K. ^{[1
,3
]}

Blanchard, Joel ^{[1
]}

Lam, Kelvin ^{[1
]}

Son, Esther Y. ^{[1
,2
,3
,5
,6
]}

Chung, Julia E. ^{[1
,2
,3
]}

Egli, Dieter ^{[1
,3
]}

Loh, Kyle M. ^{[1
]}

Carter, Ava C. ^{[1
,3
]}

Di Giorgio, Francesco P. ^{[1
,3
]}

Koszka, Kathryn ^{[1
,3
]}

Huangfu, Danwei ^{[1
]}

Akutsu, Hidenori ^{[4
]}

Liu, David R. ^{[5
,6
]}

Rubin, Lee L. ^{[1
]}

Eggan, Kevin ^{[1
,2
,3
]}

机构：

[1] Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA

[2] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA

[3] Stowers Med Inst, Kansas City, MO 64110 USA

[4] Natl Res Inst Child Hlth & Dev, Dept Reprod Biol, Setagaya Ku, Tokyo 1578535, Japan

[5] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA

[6] Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA

来源：

CELL STEM CELL | 2009年 / 5卷 / 05期

关键词：

PLURIPOTENT STEM-CELLS; HUMAN FIBROBLASTS; INDUCTION; GENERATION; MOUSE; POTENT; DIFFERENTIATION; OCT4;

D O I：

10.1016/j.stem.2009.09.012

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

The combined activity of three transcription factors can reprogram adult cells into induced pluripotent stem cells (iPSCs). However, the transgenic methods used for delivering reprogramming factors have raised concerns regarding the future utility of the resulting stem cells. These uncertainties could be overcome if each transgenic factor were replaced with a small molecule that either directly activated its expression from the somatic genome or in some way compensated for its activity. To this end, we have used high-content chemical screening to identify small molecules that can replace Sox2 in reprogramming. We show that one of these molecules functions in reprogramming by inhibiting Tgf-beta signaling in a stable and trapped intermediate cell type that forms during the process. We find that this inhibition promotes the completion of reprogramming through induction of the transcription factor Nanog.

引用

页码：491 / 503

页数：13

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