Single-cell triple omics sequencing reveals genetic, epigenetic, and transcriptomic heterogeneity in hepatocellular carcinomas.
Single-cell triple omics sequencing reveals genetic, epigenetic, and transcriptomic heterogeneity in hepatocellular carcinomas.
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单细胞三组学测序揭示肝细胞癌的遗传、表观遗传和转录组异质性
DOI：
10.1038/cr.2016.23
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发表时间：
2016-03
期刊：
影响因子：
44.1
通讯作者：
Peng J
中科院分区：
文献类型：
--
作者：
Hou Y;Guo H;Cao C;Li X;Hu B;Zhu P;Wu X;Wen L;Tang F;Huang Y;Peng J
单细胞基因组、DNA甲基组和转录组测序方法已经分别开发出来。然而，为了准确分析转录组、基因组和DNA甲基组相互调控的机制，这些组学方法需要在同一个细胞中进行。在这里，我们展示了一种单细胞三重组学测序技术，scTrio-seq，可以用于同时分析单个哺乳动物细胞的基因组拷贝数变异(CNV)、DNA甲基组和转录组。我们发现，大规模的CNV导致获得或丢失的基因组区域内基因的RNA表达的比例变化，而这些CNV通常不影响这些区域的DNA甲基化。此外，我们将scTrio-seq应用于来自人肝细胞癌组织样本的25个单个癌细胞。我们根据单个细胞的CNV、DNA甲基组或转录组确定了这些细胞中的两个亚群。我们的工作提供了一条新的途径来剖析基因组和表观基因组异质性对细胞群体内转录异质性的复杂贡献。
Single-cell genome, DNA methylome, and transcriptome sequencing methods have been separately developed. However, to accurately analyze the mechanism by which transcriptome, genome and DNA methylome regulate each other, these omic methods need to be performed in the same single cell. Here we demonstrate a single-cell triple omics sequencing technique, scTrio-seq, that can be used to simultaneously analyze the genomic copy-number variations (CNVs), DNA methylome, and transcriptome of an individual mammalian cell. We show that large-scale CNVs cause proportional changes in RNA expression of genes within the gained or lost genomic regions, whereas these CNVs generally do not affect DNA methylation in these regions. Furthermore, we applied scTrio-seq to 25 single cancer cells derived from a human hepatocellular carcinoma tissue sample. We identified two subpopulations within these cells based on CNVs, DNA methylome, or transcriptome of individual cells. Our work offers a new avenue of dissecting the complex contribution of genomic and epigenomic heterogeneities to the transcriptomic heterogeneity within a population of cells.