Single-cell triple omics sequencing reveals genetic, epigenetic, and transcriptomic heterogeneity in hepatocellular carcinomas

Single-ceU 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 demonstra...

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Published inCell research Vol. 26; no. 3; pp. 304 - 319
Main Authors Hou, Yu, Guo, Huahu, Cao, Chen, Li, Xianlong, Hu, Boqiang, Zhu, Ping, Wu, Xinglong, Wen, Lu, Tang, Fuchou, Huang, Yanyi, Peng, Jirun
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 01.03.2016
Nature Publishing Group
Subjects
631/208/176/1988
631/61/212/2019
631/61/514/1948
692/4028/67/1504/1610/4029
Animals
Biomedical and Life Sciences
Carcinoma, Hepatocellular - genetics
Cell Biology
Deoxyribonucleic acid
DNA
DNA Copy Number Variations
DNA Methylation
DNA甲基化
Epigenesis, Genetic
Epigenomics - methods
Gene Expression Profiling - methods
Genomics
Genomics - methods
Hep G2 Cells
Heterogeneity
Humans
Life Sciences
Liver Neoplasms - genetics
Male
Mice
Middle Aged
Original
original-article
Sequence Analysis, DNA
Single-Cell Analysis
Subpopulations
Transcriptome
单细胞
哺乳动物细胞
异质性
测序方法
肝细胞癌
表观遗传学
转录组
DNA methylome
HCC
CNV
scTrio-seq
transcriptome
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Summary:Single-ceU 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 om- ics 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 gen- erally 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.
Bibliography:31-1568
scTrio-seq; CNV; transcriptome; DNA methylome; HCC
Single-ceU 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 om- ics 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 gen- erally 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.
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These two authors contributed equally to this work.
ISSN:1001-0602
1748-7838
1748-7838
DOI:10.1038/cr.2016.23