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

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Kim, EJY; Anko, M-L; Flensberg, C; Majewski, IJ; Geng, F-S; Firas, J; Huang, DCS; van Delft, MF; Heath, JKDate
2018-02-13Source Title
Stem Cell ReportsPublisher
CELL PRESSUniversity of Melbourne Author/s
van Delft, Mark; Majewski, Ian; Huang, David; Heath, Joan; Geng, FansuoAffiliation
Medical Biology (W.E.H.I.)Surgery (RMH)
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Journal ArticleCitations
Kim, E. J. Y., Anko, M. -L., Flensberg, C., Majewski, I. J., Geng, F. -S., Firas, J., Huang, D. C. S., van Delft, M. F. & Heath, J. K. (2018). BAK/BAX-Mediated Apoptosis Is a Myc-Induced Roadblock to Reprogramming. STEM CELL REPORTS, 10 (2), pp.331-338. https://doi.org/10.1016/j.stemcr.2017.12.019.Access Status
Open AccessAbstract
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.
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