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Single cell multi-omics reveal intra-cell-line heterogeneity across human cancer cell lines

Author

Listed:
  • Qionghua Zhu

    (Southern University of Science and Technology
    Southern University of Science and Technology)

  • Xin Zhao

    (BGI Research
    University of Chinese Academy of Sciences)

  • Yuanhang Zhang

    (BGI Research
    University of Chinese Academy of Sciences)

  • Yanping Li

    (Southern University of Science and Technology)

  • Shang Liu

    (BGI Research)

  • Jingxuan Han

    (Southern University of Science and Technology)

  • Zhiyuan Sun

    (Southern University of Science and Technology)

  • Chunqing Wang

    (BGI Research
    University of Chinese Academy of Sciences)

  • Daqi Deng

    (Southern University of Science and Technology)

  • Shanshan Wang

    (BGI Research)

  • Yisen Tang

    (Southern University of Science and Technology)

  • Yaling Huang

    (BGI Research)

  • Siyuan Jiang

    (BGI Research
    University of Chinese Academy of Sciences)

  • Chi Tian

    (Southern University of Science and Technology)

  • Xi Chen

    (BGI Research)

  • Yue Yuan

    (BGI Research)

  • Zeyu Li

    (BGI Research
    University of Chinese Academy of Sciences)

  • Tao Yang

    (China National GeneBank)

  • Tingting Lai

    (China National GeneBank)

  • Yiqun Liu

    (China National GeneBank)

  • Wenzhen Yang

    (China National GeneBank)

  • Xuanxuan Zou

    (BGI Research
    University of Chinese Academy of Sciences)

  • Mingyuan Zhang

    (BGI Research)

  • Huanhuan Cui

    (Southern University of Science and Technology
    Southern University of Science and Technology
    Southern University of Science and Technology)

  • Chuanyu Liu

    (BGI Research)

  • Xin Jin

    (BGI Research)

  • Yuhui Hu

    (Southern University of Science and Technology
    Southern University of Science and Technology
    Southern University of Science and Technology)

  • Ao Chen

    (BGI Research
    JFL-BGI STOmics Center, Jinfeng Laboratory
    The Guangdong-Hong Kong Joint Laboratory on Immunological and Genetic Kidney Diseases)

  • Xun Xu

    (BGI Research)

  • Guipeng Li

    (Southern University of Science and Technology
    Southern University of Science and Technology
    Southern University of Science and Technology)

  • Yong Hou

    (BGI Research
    Shenzhen Key Laboratory of Single-Cell Omics, BGI-Shenzhen)

  • Longqi Liu

    (BGI Research
    BGI Research
    Shenzhen Bay Laboratory)

  • Shiping Liu

    (BGI Research
    The Guangdong-Hong Kong Joint Laboratory on Immunological and Genetic Kidney Diseases
    Shenzhen Key Laboratory of Single-Cell Omics, BGI-Shenzhen
    BGI Research)

  • Liang Fang

    (Southern University of Science and Technology
    Southern University of Science and Technology
    Southern University of Science and Technology)

  • Wei Chen

    (Southern University of Science and Technology
    Southern University of Science and Technology)

  • Liang Wu

    (BGI Research
    JFL-BGI STOmics Center, Jinfeng Laboratory
    BGI Research)

Abstract

Human cancer cell lines have long served as tools for cancer research and drug discovery, but the presence and the source of intra-cell-line heterogeneity remain elusive. Here, we perform single-cell RNA-sequencing and ATAC-sequencing on 42 and 39 human cell lines, respectively, to illustrate both transcriptomic and epigenetic heterogeneity within individual cell lines. Our data reveal that transcriptomic heterogeneity is frequently observed in cancer cell lines of different tissue origins, often driven by multiple common transcriptional programs. Copy number variation, as well as epigenetic variation and extrachromosomal DNA distribution all contribute to the detected intra-cell-line heterogeneity. Using hypoxia treatment as an example, we demonstrate that transcriptomic heterogeneity could be reshaped by environmental stress. Overall, our study performs single-cell multi-omics of commonly used human cancer cell lines and offers mechanistic insights into the intra-cell-line heterogeneity and its dynamics, which would serve as an important resource for future cancer cell line-based studies.

Suggested Citation

  • Qionghua Zhu & Xin Zhao & Yuanhang Zhang & Yanping Li & Shang Liu & Jingxuan Han & Zhiyuan Sun & Chunqing Wang & Daqi Deng & Shanshan Wang & Yisen Tang & Yaling Huang & Siyuan Jiang & Chi Tian & Xi Ch, 2023. "Single cell multi-omics reveal intra-cell-line heterogeneity across human cancer cell lines," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43991-9
    DOI: 10.1038/s41467-023-43991-9
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    References listed on IDEAS

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