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

Author

Listed:
  • Yangyang Yuan

    (Chinese Academy of Medical Sciences and Peking Union Medical College
    ShanghaiTech University
    Centre for Translational Stem Cell Biology Limited)

  • 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
    Fudan University)

  • Qiangsong Wang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Yilai Shu

    (Fudan University
    Fudan University)

  • Yu Xue

    (Huazhong University of Science and Technology
    Nanjing University Institute of Artificial Intelligence Biomedicine)

  • Pengyu Huang

    (Chinese Academy of Medical Sciences and Peking Union Medical College
    ShanghaiTech University)

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.

Suggested Citation

  • 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 & Pengyu Huan, 2022. "PIM1 promotes hepatic conversion by suppressing reprogramming-induced ferroptosis and cell cycle arrest," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32976-9
    DOI: 10.1038/s41467-022-32976-9
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    References listed on IDEAS

    as
    1. Zhonghan Li & Tariq M. Rana, 2012. "A kinase inhibitor screen identifies small-molecule enhancers of reprogramming and iPS cell generation," Nature Communications, Nature, vol. 3(1), pages 1-11, January.
    2. Alexander Hogrebe & Louise von Stechow & Dorte B. Bekker-Jensen & Brian T. Weinert & Christian D. Kelstrup & Jesper V. Olsen, 2018. "Benchmarking common quantification strategies for large-scale phosphoproteomics," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
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