BMPs functionally replace Klf4 and support efficient reprogramming of mouse fibroblasts by Oct4 alone

被引:104
作者
Chen, Jiekai [1 ]
Liu, Jing [1 ]
Yang, Jiaqi [1 ]
Chen, You [1 ]
Chen, Jing [1 ]
Ni, Su [1 ]
Song, Hong [1 ]
Zeng, Lingwen [1 ]
Ding, Ke [1 ]
Pei, Duanqing [1 ]
机构
[1] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, S China Inst Stem Cell Biol & Regenerat Med, Key Lab Regenerat Biol, Guangzhou 510530, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
Oct4; iPSCs; reprogramming; stem cell; BMPs; MET; PLURIPOTENT STEM-CELLS; GENERATION; INDUCTION; MYC;
D O I
10.1038/cr.2010.172
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Generation of induced pluripotent stem cells by defined factors has become a useful model to investigate the mechanism of reprogramming and cell fate determination. However, the precise mechanism of factor-based reprogramming remains unclear. Here, we show that Klf4 mainly acts at the initial phase of reprogramming to initiate mesenchymal-to-epithelial transition and can be functionally replaced by bone morphogenetic proteins (BMPs). BMPs boosted the efficiency of Oct4/Sox2-mediated reprogramming of mouse embryonic fibroblasts (MEFs) to similar to 1%. BMPs also promoted single-factor Oct4-based reprogramming of MEFs and tail tibial fibroblasts. Our studies clarify the contribution of Klf4 in reprogramming and establish Oct4 as a singular setter of pluripotency in differentiated cells.
引用
收藏
页码:205 / 212
页数:8
相关论文
共 25 条
[1]   Towards an Optimized Culture Medium for the Generation of Mouse Induced Pluripotent Stem Cells [J].
Chen, Jiekai ;
Liu, Jing ;
Han, Qingkai ;
Qin, Dajiang ;
Xu, Jianyong ;
Chen, You ;
Yang, Jiaqi ;
Song, Hong ;
Yang, Dongshan ;
Peng, Meixiu ;
He, Wenzhi ;
Li, Ronghui ;
Wang, Hao ;
Gan, Yi ;
Ding, Ke ;
Zeng, Lingwen ;
Lai, Liangxue ;
Esteban, Miguel A. ;
Pei, Duanqing .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (40) :31066-31072
[2]   Vitamin C Enhances the Generation of Mouse and Human Induced Pluripotent Stem Cells [J].
Esteban, Miguel Angel ;
Wang, Tao ;
Qin, Baoming ;
Yang, Jiayin ;
Qin, Dajiang ;
Cai, Jinglei ;
Li, Wen ;
Weng, Zhihui ;
Chen, Jiekai ;
Ni, Su ;
Chen, Keshi ;
Li, Yuan ;
Liu, Xiaopeng ;
Xu, Jianyong ;
Zhang, Shiqiang ;
Li, Feng ;
He, Wenzhi ;
Labuda, Krystyna ;
Song, Yancheng ;
Peterbauer, Anja ;
Wolbank, Susanne ;
Redl, Heinz ;
Zhong, Mei ;
Cai, Daozhang ;
Zeng, Lingwen ;
Pei, Duanqing .
CELL STEM CELL, 2010, 6 (01) :71-79
[3]   Reprogramming of fibroblasts into induced pluripotent stem cells with orphan nuclear receptor Esrrb [J].
Feng, Bo ;
Jiang, Jianming ;
Kraus, Petra ;
Ng, Jia-Hui ;
Heng, Jian-Chien Dominic ;
Chan, Yun-Shen ;
Yaw, Lai-Ping ;
Zhang, Weiwei ;
Loh, Yuin-Han ;
Han, Jianyong ;
Vega, Vinsensius B. ;
Cacheux-Rataboul, Valere ;
Lim, Bing ;
Lufkin, Thomas ;
Ng, Huck-Hui .
NATURE CELL BIOLOGY, 2009, 11 (02) :197-U193
[4]   A Small-Molecule Inhibitor of Tgf-β Signaling Replaces Sox2 in Reprogramming by Inducing Nanog [J].
Ichida, Justin K. ;
Blanchard, Joel ;
Lam, Kelvin ;
Son, Esther Y. ;
Chung, Julia E. ;
Egli, Dieter ;
Loh, Kyle M. ;
Carter, Ava C. ;
Di Giorgio, Francesco P. ;
Koszka, Kathryn ;
Huangfu, Danwei ;
Akutsu, Hidenori ;
Liu, David R. ;
Rubin, Lee L. ;
Eggan, Kevin .
CELL STEM CELL, 2009, 5 (05) :491-503
[5]   Embryonic stem cell-specific microRNAs promote induced pluripotency [J].
Judson, Robert L. ;
Babiarz, Joshua E. ;
Venere, Monica ;
Blelloch, Robert .
NATURE BIOTECHNOLOGY, 2009, 27 (05) :459-461
[6]   Linking the p53 tumour suppressor pathway to somatic cell reprogramming [J].
Kawamura, Teruhisa ;
Suzuki, Jotaro ;
Wang, Yunyuan V. ;
Menendez, Sergio ;
Batlle Morera, Laura ;
Raya, Angel ;
Wahl, Geoffrey M. ;
Izpisua Belmonte, Juan Carlos .
NATURE, 2009, 460 (7259) :1140-1144
[7]   Oct4-Induced Pluripotency in Adult Neural Stem Cells [J].
Kim, Jeong Beom ;
Sebastiano, Vittorio ;
Wu, Guangming ;
Arauzo-Bravo, Marcos J. ;
Sasse, Philipp ;
Gentile, Luca ;
Ko, Kinarm ;
Ruau, David ;
Ehrich, Mathias ;
van den Boom, Dirk ;
Meyer, Johann ;
Huebner, Karin ;
Bernemann, Christof ;
Ortmeier, Claudia ;
Zenke, Martin ;
Fleischmann, Bernd K. ;
Zaehres, Holm ;
Schoeler, Hans R. .
CELL, 2009, 136 (03) :411-419
[8]   A Mesenchymal-to-Epithelial Transition Initiates and Is Required for the Nuclear Reprogramming of Mouse Fibroblasts [J].
Li, Ronghui ;
Liang, Jialiang ;
Ni, Su ;
Zhou, Ting ;
Qing, Xiaobing ;
Li, Huapeng ;
He, Wenzhi ;
Chen, Jiekai ;
Li, Feng ;
Zhuang, Qiang ;
Qin, Baoming ;
Xu, Jianyong ;
Li, Wen ;
Yang, Jiayin ;
Gan, Yi ;
Qin, Dajiang ;
Feng, Shipeng ;
Song, Hong ;
Yang, Dongshan ;
Zhang, Biliang ;
Zeng, Lingwen ;
Lai, Liangxue ;
Esteban, Miguel Angel ;
Pei, Duanqing .
CELL STEM CELL, 2010, 7 (01) :51-63
[9]   Generation of Human-Induced Pluripotent Stem Cells in the Absence of Exogenous Sox2 [J].
Li, Wenlin ;
Zhou, Hongyan ;
Abujarour, Ramzey ;
Zhu, Saiyong ;
Joo, Jin Young ;
Lin, Tongxiang ;
Hao, Ergeng ;
Schoeler, Hans R. ;
Hayek, Alberto ;
Ding, Sheng .
STEM CELLS, 2009, 27 (12) :2992-3000
[10]   Reprogramming of murine fibroblasts to induced pluripotent stem cells with chemical complementation of Klf4 [J].
Lyssiotis, Costas A. ;
Foreman, Ruth K. ;
Staerk, Judith ;
Garcia, Michael ;
Mathur, Divya ;
Markoulaki, Styliani ;
Hanna, Jacob ;
Lairson, Luke L. ;
Charette, Bradley D. ;
Bouchez, Laure C. ;
Bollong, Michael ;
Kunick, Conrad ;
Brinker, Achim ;
Cho, Charles Y. ;
Schultz, Peter G. ;
Jaenisch, Rudolf .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (22) :8912-8917