Apoptotic Caspases Regulate Induction of iPSCs from Human Fibroblasts

被引：97

作者：

Li, Fang ^{[1
]}

He, Zhimin ^{[1
,3
]}

Shen, Jingping ^{[1
]}

Huang, Qian ^{[1
,4
]}

Li, Wenrong ^{[1
]}

Liu, Xinjian ^{[1
]}

He, Yujun ^{[1
]}

Wolf, Frank ^{[1
]}

Li, Chuan-Yuan ^{[1
,2
]}

机构：

[1] Univ Colorado, Sch Med, Dept Radiat Oncol, Aurora, CO 80045 USA

[2] Univ Colorado, Sch Med, Dept Pharmacol, Aurora, CO 80045 USA

[3] Cent S Univ, Canc Res Inst, Changsha 410078, Hunan, Peoples R China

[4] Shanghai Jiao Tong Univ, Sch Med, Peoples Hosp 1, Shanghai 200080, Peoples R China

来源：

CELL STEM CELL | 2010年 / 7卷 / 04期

关键词：

PLURIPOTENT STEM-CELLS; RETINOBLASTOMA PROTEIN; C-FLIP; MOUSE; GENERATION; RB; DEATH; MYC; P53; PATHWAY;

D O I：

10.1016/j.stem.2010.09.003

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

The molecular mechanisms involved in the derivation of induced pluripotent stem cells (iPSCs) from differentiated cells are poorly understood. Here we report that caspases 3 and 8, two proteases associated with apoptotic cell death, play critical roles in induction of iPSCs from human fibroblasts. Activation of caspases 3 and 8 occurs soon after transduction of iPSC-inducing transcription factors. Oct-4, a key iPSC transcription factor, is responsible for the activation. Inhibition of caspase 3 or 8 in human fibroblast cells partially or completely (respectively) prevents the induction of iPSCs. Furthermore, retinoblastoma susceptibility (Rb) protein appears to be one of the factors that act downstream of the caspases. We propose that caspases are key facilitators of nuclear reprogramming in iPSC induction.

引用

页码：508 / 520

页数：13

共 69 条

[31] Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors [J].

Kim, Jeong Beom ;

Zaehres, Holm ;

Wu, Guangming ;

Gentile, Luca ;

Ko, Kinarm ;

Sebastiano, Vittorio ;

Arauzo-Bravo, Marcos J. ;

Ruau, David ;

Han, Dong Wook ;

Zenke, Martin ;

Schoeler, Hans R. .

NATURE, 2008, 454 (7204) :646-U54

[32] Direct reprogramming of human neural stem cells by OCT4 [J].

Kim, Jeong Beom ;

Greber, Boris ;

Arauzo-Bravo, Marcos J. ;

Meyer, Johann ;

Park, Kook In ;

Zaehres, Holm ;

Schoeler, Hans R. .

NATURE, 2009, 461 (7264) :649-U93

[33] 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

[34] Caspases 3 and 7: Key mediators of mitochondrial events of apoptosis [J].

Lakhani, SA ;

Masud, A ;

Kuida, K ;

Porter, GA ;

Booth, CJ ;

Mehal, WZ ;

Inayat, I ;

Flavell, RA .

SCIENCE, 2006, 311 (5762) :847-851

[35] The Ink4/Arf locus is a barrier for iPS cell reprogramming [J].

Li, Han ;

Collado, Manuel ;

Villasante, Aranzazu ;

Strati, Katerina ;

Ortega, Sagrario ;

Canamero, Marta ;

Blasco, Maria A. ;

Serrano, Manuel .

NATURE, 2009, 460 (7259) :1136-1139

[36] Mouse Fibroblasts Lacking RB1 Function Form Spheres and Undergo Reprogramming to a Cancer Stem Cell Phenotype [J].

Liu, Yongqing ;

Clem, Brian ;

Zuba-Surma, Ewa K. ;

El-Naggar, Shahencla ;

Telang, Sucheta ;

Jenson, Alfred B. ;

Wang, Yali ;

Shao, Hui ;

Ratajczak, Mariusz Z. ;

Chesney, Jason ;

Dean, Douglas C. .

CELL STEM CELL, 2009, 4 (04) :336-347

[37] Generation of human induced pluripotent stem cells from dermal fibroblasts [J].

Lowry, W. E. ;

Richter, L. ;

Yachechko, R. ;

Pyle, A. D. ;

Tchieu, J. ;

Sridharan, R. ;

Clark, A. T. ;

Plath, K. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (08) :2883-2888

[38] Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution [J].

Maherali, Nimet ;

Sridharan, Rupa ;

Xie, Wei ;

Utikal, Jochen ;

Eminli, Sarah ;

Arnold, Katrin ;

Stadtfeld, Matthias ;

Yachechko, Robin ;

Tchieu, Jason ;

Jaenisch, Rudolf ;

Plath, Kathrin ;

Hochedlinger, Konrad .

CELL STEM CELL, 2007, 1 (01) :55-70

[39] Guidelines and Techniques for the Generation of Induced Pluripotent Stem Cells [J].

Maherali, Nimet ;

Hochedlinger, Konrad .

CELL STEM CELL, 2008, 3 (06) :595-605

[40] A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity [J].

Marion, Rosa M. ;

Strati, Katerina ;

Li, Han ;

Murga, Matilde ;

Blanco, Raquel ;

Ortega, Sagrario ;

Fernandez-Capetillo, Oscar ;

Serrano, Manuel ;

Blasco, Maria A. .

NATURE, 2009, 460 (7259) :1149-1153

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