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

被引：450

作者：

Hou, Yu ^{[1
]}

Guo, Huahu ^{[2
,3
,4
]}

Cao, Chen ^{[1
]}

Li, Xianlong ^{[1
]}

Hu, Boqiang ^{[1
]}

Zhu, Ping ^{[1
,6
]}

Wu, Xinglong ^{[1
,6
]}

Wen, Lu ^{[1
]}

Tang, Fuchou ^{[1
,5
,6
,7
]}

Huang, Yanyi ^{[1
,6
,8
]}

Peng, Jirun ^{[2
,3
,4
]}

机构：

[1] Peking Univ, Coll Life Sci, Biodynam Opt Imaging Ctr, Beijing 100871, Peoples R China

[2] Capital Med Univ, Beijing Shijitan Hosp, Dept Surg, Beijing 100038, Peoples R China

[3] Peking Univ, Sch Clin Med 9, Beijing 100038, Peoples R China

[4] Capital Med Univ, Sch Oncol, Beijing 100038, Peoples R China

[5] Peking Univ, Minist Educ, Key Lab Cell Proliferat & Differentiat, Beijing 100871, Peoples R China

[6] Peking Tsinghua Ctr Life Sci, Beijing 100084, Peoples R China

[7] Ctr Mol & Translat Med, Beijing 100101, Peoples R China

[8] Peking Univ, Coll Engn, Beijing 100871, Peoples R China

来源：

CELL RESEARCH | 2016年 / 26卷 / 03期

基金：

中国国家自然科学基金;

关键词：

scTrio-seq; CNV; transcriptome; DNA methylome; HCC; DNA METHYLATION LANDSCAPE; COPY NUMBER VARIATION; MESSENGER-RNA-SEQ; CANCER EPIGENETICS; GENOME; EXPRESSION; LINEAGE; TISSUES; EMBRYOS; TMEM16A;

D O I：

10.1038/cr.2016.23

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：304 / 319

页数：16

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