Single cell multi-omics reveal intra-cell-line heterogeneity across human cancer cell lines
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Published:2023-12-09
Issue:1
Volume:14
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Zhu QionghuaORCID, Zhao Xin, Zhang Yuanhang, Li Yanping, Liu Shang, Han Jingxuan, Sun Zhiyuan, Wang Chunqing, Deng Daqi, Wang Shanshan, Tang Yisen, Huang Yaling, Jiang Siyuan, Tian ChiORCID, Chen Xi, Yuan Yue, Li ZeyuORCID, Yang TaoORCID, Lai Tingting, Liu Yiqun, Yang Wenzhen, Zou Xuanxuan, Zhang Mingyuan, Cui HuanhuanORCID, Liu ChuanyuORCID, Jin XinORCID, Hu YuhuiORCID, Chen AoORCID, Xu XunORCID, Li GuipengORCID, Hou Yong, Liu LongqiORCID, Liu ShipingORCID, Fang LiangORCID, Chen WeiORCID, Wu LiangORCID
Abstract
AbstractHuman 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.
Funder
Chinese Ministry of Science and Technology | Department of S and T for Social Development Shenzhen Science and Technology Innovation Commission National Natural Science Foundation of China Natural Science Foundation of Guangdong Province
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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