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

Fu, Xiuling1; Zhuang, Qiang1; Babarinde, Isaac A.1; Shi, Liyang1; Ma, Gang1; Hu, Haoqing2; Li, Yuhao1; Chen, Jiao1; Xiao, Zhen1; Deng, Boping1; Sun, Li1; Jauch, Ralf2,3; Hutchins, Andrew P.1

2023-07-14

10.1038/s41420-023-01533-8

CELL DEATH DISCOVERY   影响因子和分区

2058-7716

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.

SCI

英语

第一 ; 通讯

National Natural Science Foundation of China["32150710521","32270597"] ; Shenzhen Innovation Committee of Science and Technology[JCYJ20200109141018712] ; Health and Medical Research Fund["06174006","08192886"] ; Research Grants Council of Hong Kong General Research Fund (RGC/GRF)["17128918","17101120","17106622"] ; null[C7064-22G]

Cell Biology

Cell Biology

WOS:001028783200001

SPRINGERNATURE

2-s2.0-85165302876

Web of Science

1.Southern Univ Sci & Technol, Sch Life Sci, Dept Syst Biol, Shenzhen 518055, Peoples R China
2.Univ Hong Kong, Li Ka Shing Fac Med, Sch Biomed Sci, Hong Kong, Peoples R China
3.Ctr Translat Stem Cell Biol, Hong Kong, Peoples R China

Fu, Xiuling,Zhuang, Qiang,Babarinde, Isaac A.,et al. Restricting epigenetic activity promotes the reprogramming of transformed cells to pluripotency in a line-specific manner[J]. CELL DEATH DISCOVERY,2023,9(1).

Fu, Xiuling.,Zhuang, Qiang.,Babarinde, Isaac A..,Shi, Liyang.,Ma, Gang.,...&Hutchins, Andrew P..(2023).Restricting epigenetic activity promotes the reprogramming of transformed cells to pluripotency in a line-specific manner.CELL DEATH DISCOVERY,9(1).

Fu, Xiuling,et al."Restricting epigenetic activity promotes the reprogramming of transformed cells to pluripotency in a line-specific manner".CELL DEATH DISCOVERY 9.1(2023).