BAK/BAX-Mediated Apoptosis Is a Myc-Induced Roadblock to Reprogramming.

Autor:	Kim EJY; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia., Anko ML; Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Development and Stem Cells Program, Monash University, Clayton, VIC 3800, Australia., Flensberg C; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia., Majewski IJ; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia., Geng FS; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia., Firas J; Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Development and Stem Cells Program, Monash University, Clayton, VIC 3800, Australia., Huang DCS; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia., van Delft MF; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia. Electronic address: vandelft@wehi.edu.au., Heath JK; The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia. Electronic address: joan.heath@wehi.edu.au.
Jazyk:	angličtina
Zdroj:	Stem cell reports [Stem Cell Reports] 2018 Feb 13; Vol. 10 (2), pp. 331-338. Date of Electronic Publication: 2018 Jan 18.
DOI:	10.1016/j.stemcr.2017.12.019
Abstrakt:	Despite intensive efforts to optimize the process, reprogramming differentiated cells to induced pluripotent stem cells (iPSCs) remains inefficient. The most common combination of transcription factors employed comprises OCT4, KLF4, SOX2, and MYC (OKSM). If MYC is omitted (OKS), reprogramming efficiency is reduced further. Cells must overcome several obstacles to reach the pluripotent state, one of which is apoptosis. To directly determine how extensively apoptosis limits reprogramming, we exploited mouse embryonic fibroblasts (MEFs) lacking the two essential mediators of apoptosis, BAK and BAX. Our results show that reprogramming is enhanced in MEFs deficient in BAK and BAX, but only when MYC is part of the reprogramming cocktail. Thus, the propensity for Myc overexpression to elicit apoptosis creates a significant roadblock to reprogramming under OKSM conditions. Our results suggest that blocking apoptosis during reprogramming may enhance the derivation of iPSCs for research and therapeutic purposes. (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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