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

[1]

An B, 1996, CANCER RES, V56, P438

[2] Chromatin signatures of pluripotent cell lines [J].

Azuara, V ;

Perry, P ;

Sauer, S ;

Spivakov, M ;

Jorgensen, HF ;

John, RM ;

Gouti, M ;

Casanova, M ;

Warnes, G ;

Merkenschlager, M ;

Fisher, AG .

NATURE CELL BIOLOGY, 2006, 8 (05) :532-U189

[3] THE REGION OF THE HPV E7 ONCOPROTEIN HOMOLOGOUS TO ADENOVIRUS E1A AND SV40 LARGE T-ANTIGEN CONTAINS SEPARATE DOMAINS FOR RB BINDING AND CASEIN KINASE-II PHOSPHORYLATION [J].

BARBOSA, MS ;

EDMONDS, C ;

FISHER, C ;

SCHILLER, JT ;

LOWY, DR ;

VOUSDEN, KH .

EMBO JOURNAL, 1990, 9 (01) :153-160

[4] Reprogramming towards pluripotency requires AID-dependent DNA demethylation [J].

Bhutani, Nidhi ;

Brady, Jennifer J. ;

Damian, Mara ;

Sacco, Alessandra ;

Corbel, Stephane Y. ;

Blau, Helen M. .

NATURE, 2010, 463 (7284) :1042-U57

[5] Generation of induced pluripotent stem cells in the absence of drug selection [J].

Blelloch, Robert ;

Venere, Monica ;

Yen, Jonathan ;

Ramalho-Santos, Miguel .

CELL STEM CELL, 2007, 1 (03) :245-247

[6] Sequential expression of pluripotency markers during direct reprogramming of mouse somatic cells [J].

Brambrink, Tobias ;

Foreman, Ruth ;

Welstead, G. Grant ;

Lengner, Christopher J. ;

Wernig, Marius ;

Suh, Heikyung ;

Jaenisch, Rudolf .

CELL STEM CELL, 2008, 2 (02) :151-159

[7] Signalling, cell cycle and pluripotency in embryonic stem cells [J].

Burdon, T ;

Smith, A ;

Savatier, P .

TRENDS IN CELL BIOLOGY, 2002, 12 (09) :432-438

[8] Ablation of the Retinoblastoma gene family deregulates G1 control causing immortalization and increased cell turnover under growth-restricting conditions [J].

Dannenberg, JH ;

van Rossum, A ;

Schuijff, L ;

Riele, HT .

GENES & DEVELOPMENT, 2000, 14 (23) :3051-3064

[9] Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2 [J].

Danwei Huangfu ;

Osafune, Kenji ;

Maehr, Rene ;

Guo, Wenjun ;

Eijkelenboom, Astrid ;

Chen, Shuibing ;

Muhlestein, Whitney ;

Melton, Douglas A. .

NATURE BIOTECHNOLOGY, 2008, 26 (11) :1269-1275

[10] Ronin is essential for embryogenesis and the pluripotency of mouse embryonic stem cells [J].

Dejosez, Marion ;

Krumenacker, Joshua S. ;

Zitur, Laura Jo ;

Passeri, Marco ;

Chu, Li-Fang ;

Zhou Songyang ;

Thomson, James A. ;

Zwaka, Thomas P. .

CELL, 2008, 133 (07) :1162-1174

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