BAK/BAX-mediated apoptosis is a Myc-induced roadblock to reprogramming
- Author(s)
- Kim, EJY; Anko, ML; Flensberg, C; Majewski, IJ; Geng, FS; Firas, J; Huang, DCS; van Delft, MF; Heath, JK;
- Details
- Publication Year 2018-01-17,Volume 10,Issue #2,Page 331-338
- Journal Title
- Stem Cell Reports
- Publication Type
- Journal Article
- 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.
- Publisher
- Elsevier
- Research Division(s)
- Cancer And Haematology; Development And Cancer
- PubMed ID
- 29358089
- Publisher's Version
- https://doi.org/10.1016/j.stemcr.2017.12.019
- Open Access at Publisher's Site
https://doi.org/10.1016/j.stemcr.2017.12.019- NHMRC Grants
- NHMRC/1043092, NHMRC/1022870, NHMRC/487922,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2018-02-27 12:35:05
Last Modified: 2018-02-27 01:20:57