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

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 t...

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Published inNature communications Vol. 14; no. 1; pp. 8170 - 21
Main Authors Zhu, Qionghua, 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, Chi, Chen, Xi, Yuan, Yue, Li, Zeyu, Yang, Tao, Lai, Tingting, Liu, Yiqun, Yang, Wenzhen, Zou, Xuanxuan, Zhang, Mingyuan, Cui, Huanhuan, Liu, Chuanyu, Jin, Xin, Hu, Yuhui, Chen, Ao, Xu, Xun, Li, Guipeng, Hou, Yong, Liu, Longqi, Liu, Shiping, Fang, Liang, Chen, Wei, Wu, Liang
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 09.12.2023
Nature Publishing Group
Nature Portfolio
Subjects
45/91
631/208/177
631/208/69
631/337/2019
Biological analysis
Cancer
Cell Line, Tumor
Copy number
Deoxyribonucleic acid
DNA
DNA Copy Number Variations
Environmental stress
Epigenetics
Epigenomics
Gene sequencing
Heterogeneity
Humanities and Social Sciences
Humans
Hypoxia
multidisciplinary
Multiomics
Neoplasms - genetics
Science
Science (multidisciplinary)
Transcriptome
Transcriptomics
Tumor cell lines
Variation
Online AccessGet full text

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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. Intra-cell line heterogeneity remains to be characterized. Here, the use of single multi-omics on a large panel of human cell lines identifies copy number variation, epigenetic variation and extrachromosomal DNA distribution as the main contributors to intra-cell line heterogeneity.
AbstractList 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. Intra-cell line heterogeneity remains to be characterized. Here, the use of single multi-omics on a large panel of human cell lines identifies copy number variation, epigenetic variation and extrachromosomal DNA distribution as the main contributors to intra-cell line heterogeneity.
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.Intra-cell line heterogeneity remains to be characterized. Here, the use of single multi-omics on a large panel of human cell lines identifies copy number variation, epigenetic variation and extrachromosomal DNA distribution as the main contributors to intra-cell line heterogeneity.
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.
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.
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.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.
ArticleNumber 8170
Author Chen, Xi
Chen, Ao
Yang, Tao
Li, Yanping
Xu, Xun
Liu, Shiping
Jin, Xin
Hou, Yong
Yuan, Yue
Hu, Yuhui
Han, Jingxuan
Wu, Liang
Zhang, Mingyuan
Tang, Yisen
Jiang, Siyuan
Yang, Wenzhen
Cui, Huanhuan
Zhu, Qionghua
Deng, Daqi
Zou, Xuanxuan
Liu, Shang
Liu, Yiqun
Wang, Shanshan
Zhao, Xin
Liu, Longqi
Wang, Chunqing
Chen, Wei
Huang, Yaling
Tian, Chi
Li, Zeyu
Li, Guipeng
Zhang, Yuanhang
Liu, Chuanyu
Sun, Zhiyuan
Lai, Tingting
Fang, Liang
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/38071219$$D View this record in MEDLINE/PubMed
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Snippet 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...
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...
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SubjectTerms 45/91
631/208/177
631/208/69
631/337/2019
Biological analysis
Cancer
Cell Line, Tumor
Copy number
Deoxyribonucleic acid
DNA
DNA Copy Number Variations
Environmental stress
Epigenetics
Epigenomics
Gene sequencing
Heterogeneity
Humanities and Social Sciences
Humans
Hypoxia
multidisciplinary
Multiomics
Neoplasms - genetics
Science
Science (multidisciplinary)
Transcriptome
Transcriptomics
Tumor cell lines
Variation
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Title Single cell multi-omics reveal intra-cell-line heterogeneity across human cancer cell lines
URI https://link.springer.com/article/10.1038/s41467-023-43991-9
https://www.ncbi.nlm.nih.gov/pubmed/38071219
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