Single-cell analysis of lung adenocarcinoma cell lines reveals diverse expression patterns of individual cells invoked by a molecular target drug treatment.
Single-cell analysis of lung adenocarcinoma cell lines reveals diverse expression patterns of individual cells invoked by a molecular target drug treatment.
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DOI：
10.1186/s13059-015-0636-y
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发表时间：
2015-04-03
期刊：
影响因子：
12.3
通讯作者：
Suzuki Y
中科院分区：
文献类型：
--
作者：
Suzuki A;Matsushima K;Makinoshima H;Sugano S;Kohno T;Tsuchihara K;Suzuki Y
为了了解单个癌细胞的异质性行为，研究基因表达水平以及不同单个细胞之间的差异是至关重要的。下一代测序相关技术的最新进展使我们能够对一系列肺腺癌细胞系进行单细胞RNA-Seq分析。我们分析了来自7个细胞系的总共336个单细胞RNA-Seq文库。关于平均表达水平和个体细胞之间的相对基因表达差异，结果是高度稳健的。基因表达的多样性取决于基因和途径。对用多酪氨酸激酶抑制剂凡德他尼处理的单个细胞的分析表明，虽然核糖体基因和许多其他所谓的管家基因在药物处理期间降低了其相对表达多样性，但凡德他尼直接靶向的基因EGFR和RET基因保持不变。这些基因的严格转录控制可能不允许其表达随药物治疗或在细胞获得耐药性期间发生塑性变化。此外，我们发现癌症相关基因的基因表达模式有时比基于创始细胞的预期更多样化。此外，我们发现这种多样性在正常状态下偶尔是潜伏的，在药物治疗后最初变得明显。基因表达差异的特征模式，这将不会被散装细胞的转录组分析揭示，也可能发挥重要作用时，细胞获得耐药性，也许是通过提供一个细胞库的基因表达程序。本文的在线版本（doi：10.1186/s13059-015-0636-y）包含补充材料，可供授权用户使用。
To understand the heterogeneous behaviors of individual cancer cells, it is essential to investigate gene expression levels as well as their divergence between different individual cells. Recent advances in next-generation sequencing-related technologies have enabled us to conduct a single-cell RNA-Seq analysis of a series of lung adenocarcinoma cell lines. We analyze a total of 336 single-cell RNA-Seq libraries from seven cell lines. The results are highly robust regarding both average expression levels and the relative gene expression differences between individual cells. Gene expression diversity is characteristic depending on genes and pathways. Analyses of individual cells treated with the multi-tyrosine kinase inhibitor vandetanib reveal that, while the ribosomal genes and many other so-called house-keeping genes reduce their relative expression diversity during the drug treatment, the genes that are directly targeted by vandetanib, the EGFR and RET genes, remain constant. Rigid transcriptional control of these genes may not allow plastic changes of their expression with the drug treatment or during the cellular acquisition of drug resistance. Additionally, we find that the gene expression patterns of cancer-related genes are sometimes more diverse than expected based on the founder cells. Furthermore, we find that this diversity is occasionally latent in a normal state and initially becomes apparent after the drug treatment. Characteristic patterns in gene expression divergence, which would not be revealed by transcriptome analysis of bulk cells, may also play important roles when cells acquire drug resistance, perhaps by providing a cellular reservoir for gene expression programs. The online version of this article (doi:10.1186/s13059-015-0636-y) contains supplementary material, which is available to authorized users.
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影响因子：
64.8
作者：
Shalek, Alex K.;Satija, Rahul;Shuga, Joe;Trombetta, John J.;Gennert, Dave;Lu, Diana;Chen, Peilin;Gertner, Rona S.;Gaublomme, Jellert T.;Yosef, Nir;Schwartz, Schraga;Fowler, Brian;Weaver, Suzanne;Wang, Jing;Wang, Xiaohui;Ding, Ruihua;Raychowdhury, Raktima;Friedman, Nir;Hacohen, Nir;Park, Hongkun;May, Andrew P.;Regev, Aviv
通讯作者：
Regev, Aviv
影响因子：
64.8
作者：
通讯作者：
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影响因子：
46.9
作者：
通讯作者：
--
影响因子：
82.9
作者：
Kohno T;Ichikawa H;Totoki Y;Yasuda K;Hiramoto M;Nammo T;Sakamoto H;Tsuta K;Furuta K;Shimada Y;Iwakawa R;Ogiwara H;Oike T;Enari M;Schetter AJ;Okayama H;Haugen A;Skaug V;Chiku S;Yamanaka I;Arai Y;Watanabe S;Sekine I;Ogawa S;Harris CC;Tsuda H;Yoshida T;Yokota J;Shibata T
通讯作者：
Shibata T
影响因子：
46.9
作者：
通讯作者：
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