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

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 Chen, Yue Yuan, Zeyu Li, Tao Yang, Tingting Lai, Yiqun Liu, Wenzhen Yang, Xuanxuan Zou, Mingyuan Zhang, Huanhuan Cui, Chuanyu Liu, Xin Jin, Yuhui Hu, Ao Chen, Xun Xu, Guipeng Li, Yong Hou, Longqi Liu (), Shiping Liu (), Liang Fang (), Wei Chen () and Liang Wu ()
Additional contact information
Qionghua Zhu: Southern University of Science and Technology
Xin Zhao: BGI Research
Yuanhang Zhang: BGI Research
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
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
Chi Tian: Southern University of Science and Technology
Xi Chen: BGI Research
Yue Yuan: BGI Research
Zeyu Li: BGI Research
Tao Yang: China National GeneBank
Tingting Lai: China National GeneBank
Yiqun Liu: China National GeneBank
Wenzhen Yang: China National GeneBank
Xuanxuan Zou: BGI Research
Mingyuan Zhang: BGI Research
Huanhuan Cui: Southern University of Science and Technology
Chuanyu Liu: BGI Research
Xin Jin: BGI Research
Yuhui Hu: Southern University of Science and Technology
Ao Chen: BGI Research
Xun Xu: BGI Research
Guipeng Li: Southern University of Science and Technology
Yong Hou: BGI Research
Longqi Liu: BGI Research
Shiping Liu: BGI Research
Liang Fang: Southern University of Science and Technology
Wei Chen: Southern University of Science and Technology
Liang Wu: BGI Research

Nature Communications, 2023, vol. 14, issue 1, 1-21

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-43991-9

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