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Integrated profiling of human pancreatic cancer organoids reveals chromatin accessibility features associated with drug sensitivity

Author

Listed:
  • Xiaohan Shi

    (Second Military Medical University (Naval Medical University))

  • Yunguang Li

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Qiuyue Yuan

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Shijie Tang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Shiwei Guo

    (Second Military Medical University (Naval Medical University))

  • Yehan Zhang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Juan He

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Xiaoyu Zhang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Ming Han

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Zhuang Liu

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Yiqin Zhu

    (Chinese Academy of Sciences)

  • Suizhi Gao

    (Second Military Medical University (Naval Medical University))

  • Huan Wang

    (Second Military Medical University (Naval Medical University))

  • Xiongfei Xu

    (Second Military Medical University (Naval Medical University))

  • Kailian Zheng

    (Second Military Medical University (Naval Medical University))

  • Wei Jing

    (Second Military Medical University (Naval Medical University))

  • Luonan Chen

    (Chinese Academy of Sciences
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences, Chinese Academy of Sciences
    Guangdong Institute of Intelligence Science and Technology, Hengqin)

  • Yong Wang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences, Chinese Academy of Sciences)

  • Gang Jin

    (Second Military Medical University (Naval Medical University))

  • Dong Gao

    (Chinese Academy of Sciences
    Chinese Academy of Sciences)

Abstract

Chromatin accessibility plays an essential role in controlling cellular identity and the therapeutic response of human cancers. However, the chromatin accessibility landscape and gene regulatory network of pancreatic cancer are largely uncharacterized. Here, we integrate the chromatin accessibility profiles of 84 pancreatic cancer organoid lines with whole-genome sequencing data, transcriptomic sequencing data and the results of drug sensitivity analysis of 283 epigenetic-related chemicals and 5 chemotherapeutic drugs. We identify distinct transcription factors that distinguish molecular subtypes of pancreatic cancer, predict numerous chromatin accessibility peaks associated with gene regulatory networks, discover regulatory noncoding mutations with potential as cancer drivers, and reveal the chromatin accessibility signatures associated with drug sensitivity. These results not only provide the chromatin accessibility atlas of pancreatic cancer but also suggest a systematic approach to comprehensively understand the gene regulatory network of pancreatic cancer in order to advance diagnosis and potential personalized medicine applications.

Suggested Citation

  • Xiaohan Shi & Yunguang Li & Qiuyue Yuan & Shijie Tang & Shiwei Guo & Yehan Zhang & Juan He & Xiaoyu Zhang & Ming Han & Zhuang Liu & Yiqin Zhu & Suizhi Gao & Huan Wang & Xiongfei Xu & Kailian Zheng & W, 2022. "Integrated profiling of human pancreatic cancer organoids reveals chromatin accessibility features associated with drug sensitivity," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29857-6
    DOI: 10.1038/s41467-022-29857-6
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    References listed on IDEAS

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