Restricting epigenetic activity promotes the reprogramming of transformed cells to pluripotency in a line-specific manner

Somatic cell reprogramming and oncogenic transformation share surprisingly similar features, yet transformed cells are resistant to reprogramming. Epigenetic barriers must block transformed cells from reprogramming, but the nature of those barriers is unclear. In this study, we generated a systemati...

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Bibliographic Details
Published in:Cell death discovery 2023-07, Vol.9 (1), p.245-245, Article 245
Main Authors: Fu, Xiuling, Zhuang, Qiang, Babarinde, Isaac A., Shi, Liyang, Ma, Gang, Hu, Haoqing, Li, Yuhao, Chen, Jiao, Xiao, Zhen, Deng, Boping, Sun, Li, Jauch, Ralf, Hutchins, Andrew P.
Format: Article
Language:English
Subjects:
631/136/142
631/532/2435
631/67/71
Apoptosis
Biochemistry
Biomedical and Life Sciences
Cancer
Cell Biology
Cell cycle
Cell Cycle Analysis
Cell lines
Efficiency
Embryo fibroblasts
Epigenetics
Genes
Genetic transformation
KLF4 protein
Leukemia
Life Sciences
Myc protein
Oct-4 protein
Pluripotency
Stem Cells
Transformed cells
Transgenes
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Summary:Somatic cell reprogramming and oncogenic transformation share surprisingly similar features, yet transformed cells are resistant to reprogramming. Epigenetic barriers must block transformed cells from reprogramming, but the nature of those barriers is unclear. In this study, we generated a systematic panel of transformed mouse embryonic fibroblasts (MEFs) using oncogenic transgenes and discovered transformed cell lines compatible with reprogramming when transfected with Oct4 / Sox2 / Klf4 / Myc . By comparing the reprogramming-capable and incapable transformed lines we identified multiple stages of failure in the reprogramming process. Some transformed lines failed at an early stage, whilst other lines seemed to progress through a conventional reprogramming process. Finally, we show that MEK inhibition overcomes one critical reprogramming barrier by indirectly suppressing a hyperacetylated active epigenetic state. This study reveals that diverse epigenetic barriers underly resistance to reprogramming of transformed cells.
ISSN:2058-7716
2058-7716
DOI:10.1038/s41420-023-01533-8