PIM1 promotes hepatic conversion by suppressing reprogramming-induced ferroptosis and cell cycle arrest

Yangyang Yuan, Chenwei Wang, Xuran Zhuang, Shaofeng Lin, Miaomiao Luo, Wankun Deng, Jiaqi Zhou, Lihui Liu, Lina Mao, Wenbo Peng, Jian Chen, Qiangsong Wang, Yilai Shu (), Yu Xue () and Pengyu Huang ()
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Yangyang Yuan: Chinese Academy of Medical Sciences and Peking Union Medical College
Chenwei Wang: Huazhong University of Science and Technology
Xuran Zhuang: ShanghaiTech University
Shaofeng Lin: Huazhong University of Science and Technology
Miaomiao Luo: Chinese Academy of Medical Sciences and Peking Union Medical College
Wankun Deng: Huazhong University of Science and Technology
Jiaqi Zhou: Huazhong University of Science and Technology
Lihui Liu: Chinese Academy of Medical Sciences and Peking Union Medical College
Lina Mao: Chinese Academy of Medical Sciences and Peking Union Medical College
Wenbo Peng: ShanghaiTech University
Jian Chen: Fudan University
Qiangsong Wang: Chinese Academy of Medical Sciences and Peking Union Medical College
Yilai Shu: Fudan University
Yu Xue: Huazhong University of Science and Technology
Pengyu Huang: Chinese Academy of Medical Sciences and Peking Union Medical College

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: Abstract Protein kinase-mediated phosphorylation plays a critical role in many biological processes. However, the identification of key regulatory kinases is still a great challenge. Here, we develop a trans-omics-based method, central kinase inference, to predict potentially key kinases by integrating quantitative transcriptomic and phosphoproteomic data. Using known kinases associated with anti-cancer drug resistance, the accuracy of our method denoted by the area under the curve is 5.2% to 29.5% higher than Kinase-Substrate Enrichment Analysis. We further use this method to analyze trans-omic data in hepatocyte maturation and hepatic reprogramming of human dermal fibroblasts, uncovering 5 kinases as regulators in the two processes. Further experiments reveal that a serine/threonine kinase, PIM1, promotes hepatic conversion and protects human dermal fibroblasts from reprogramming-induced ferroptosis and cell cycle arrest. This study not only reveals new regulatory kinases, but also provides a helpful method that might be extended to predict central kinases involved in other biological processes.

Date: 2022
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DOI: 10.1038/s41467-022-32976-9

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