Document Detail


Apoptotic caspases regulate induction of iPSCs from human fibroblasts.
MedLine Citation:
PMID:  20887956     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Fang Li; Zhimin He; Jingping Shen; Qian Huang; Wenrong Li; Xinjian Liu; Yujun He; Frank Wolf; Chuan-Yuan Li
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Cell stem cell     Volume:  7     ISSN:  1875-9777     ISO Abbreviation:  Cell Stem Cell     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-04     Completed Date:  2011-03-16     Revised Date:  2012-05-07    
Medline Journal Info:
Nlm Unique ID:  101311472     Medline TA:  Cell Stem Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  508-20     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis*
Caspase 3 / metabolism*
Caspase 8 / metabolism*
Fibroblasts / cytology*,  metabolism*
Humans
Induced Pluripotent Stem Cells*
Nuclear Reprogramming
Grant Support
ID/Acronym/Agency:
CA131408/CA/NCI NIH HHS; CA136748/CA/NCI NIH HHS; R01 CA131408-02/CA/NCI NIH HHS; R01 CA131408-03/CA/NCI NIH HHS; R01 CA136748-02/CA/NCI NIH HHS; R01 CA136748-03/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 8
Comments/Corrections

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