2. Academic Validation
  3. PIM1 promotes hepatic conversion by suppressing reprogramming-induced ferroptosis and cell cycle arrest

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

  • Nat Commun. 2022 Sep 6;13(1):5237. doi: 10.1038/s41467-022-32976-9.
Yangyang Yuan  # 1 2 3,  Chenwei Wang  # 4,  Xuran Zhuang  # 2,  Shaofeng Lin  # 4,  Miaomiao Luo  # 1,  Wankun Deng 4,  Jiaqi Zhou 4,  Lihui Liu 1,  Lina Mao 1,  Wenbo Peng 2,  Jian Chen 5 6,  Qiangsong Wang 1,  Yilai Shu 7 8,  Yu Xue 9 10,  Pengyu Huang 11 12
Affiliations

Affiliations

  • 1 Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300192, China.
  • 2 School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
  • 3 Centre for Translational Stem Cell Biology Limited, Hong Kong, 999077, China.
  • 4 MOE Key Laboratory of Molecular Biophysics, Hubei Bioinformatics and Molecular Imaging Key Laboratory, Center for Artificial Intelligence Biology, Institute of Artificial Intelligence, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, China.
  • 5 ENT institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200031, China.
  • 6 NHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai, 200031, China.
  • 7 ENT institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200031, China. yilai_shu@fudan.edu.cn.
  • 8 NHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai, 200031, China. yilai_shu@fudan.edu.cn.
  • 9 MOE Key Laboratory of Molecular Biophysics, Hubei Bioinformatics and Molecular Imaging Key Laboratory, Center for Artificial Intelligence Biology, Institute of Artificial Intelligence, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, China. xueyu@hust.edu.cn.
  • 10 Nanjing University Institute of Artificial Intelligence Biomedicine, Nanjing, Jiangsu, 210031, China. xueyu@hust.edu.cn.
  • 11 Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300192, China. huangpengyu@yeah.net.
  • 12 School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China. huangpengyu@yeah.net.
  • # Contributed equally.
PMID: 36068222 DOI: 10.1038/s41467-022-32976-9
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.

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