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

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    Author
    Kim, EJY; Anko, M-L; Flensberg, C; Majewski, IJ; Geng, F-S; Firas, J; Huang, DCS; van Delft, MF; Heath, JK
    Date
    2018-02-13
    Source Title
    Stem Cell Reports
    Publisher
    CELL PRESS
    University of Melbourne Author/s
    van Delft, Mark; Majewski, Ian; Huang, David; Heath, Joan; Geng, Fansuo
    Affiliation
    Medical Biology (W.E.H.I.)
    Surgery (RMH)
    Metadata
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    Document Type
    Journal Article
    Citations
    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 Access
    URI
    http://hdl.handle.net/11343/253104
    DOI
    10.1016/j.stemcr.2017.12.019
    Abstract
    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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