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

Publication date: Available online 18 January 2018 Source:Stem Cell Reports Author(s): Esther J.Y. Kim, Minna-Liisa Anko, Christoffer Flensberg, Ian J. Majewski, Fan-Suo Geng, Jaber Firas, David C.S. Huang, Mark F. van Delft, Joan K. Heath 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. Teaser In this article, Heath, van Delft, and colleagues show that mitochondrial apoptosis limits OKSM-mediated reprogramming of MEFs. Not only is reprogramming of MEFs lacking the two essential mediators of mitochondrial apoptosis...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research