Single-cell multiomics sequencing and analyses of human colorectal cancer

被引：257

作者：

Bian, Shuhui ^{[1
,2
,3
,4
]}

Hou, Yu ^{[1
,2
,3
]}

Zhou, Xin ^{[5
]}

Li, Xianlong ^{[1
,2
,3
]}

Yong, Jun ^{[1
,6
]}

Wang, Yicheng ^{[1
,2
,3
]}

Wang, Wendong ^{[5
]}

Yan, Jia ^{[1
,2
,3
]}

Hu, Boqiang ^{[1
,2
,3
]}

Guo, Hongshan ^{[1
,2
,3
]}

Wang, Jilian ^{[5
]}

Gao, Shuai ^{[1
,2
,3
]}

Mao, Yunuo ^{[1
,2
,3
]}

Dong, Ji ^{[1
,2
,3
]}

Zhu, Ping ^{[1
,2
,3
,4
]}

Xiu, Dianrong ^{[5
]}

Yan, Liying ^{[1
,6
]}

Wen, Lu ^{[1
,2
,3
]}

Qiao, Jie ^{[1
,4
,6
,7
]}

Tang, Fuchou ^{[1
,2
,3
,4
]}

Fu, Wei ^{[5
]}

机构：

[1] Peking Univ, Hosp 3, Dept Obstet & Gynecol, Beijing Adv Innovat Ctr Genom,Coll Life Sci, Beijing 100871, Peoples R China

[2] Minist Educ, Key Lab Cell Proliferat & Differentiat, Biomed Pioneering Innovat Ctr, Beijing 100871, Peoples R China

[3] Minist Educ, Key Lab Cell Proliferat & Differentiat, Ctr Reprod Med, Beijing 100871, Peoples R China

[4] Peking Univ, Acad Adv Interdisciplinary Studies, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China

[5] Peking Univ, Hosp 3, Dept Gen Surg, Beijing 100191, Peoples R China

[6] Minist Educ, Key Lab Assisted Reprod, Beijing 100191, Peoples R China

[7] Beijing Key Lab Reprod Endocrinol & Assisted Repr, Beijing 100191, Peoples R China

来源：

SCIENCE | 2018年 / 362卷 / 6418期

基金：

中国国家自然科学基金;

关键词：

HETEROGENEITY; TRANSCRIPTOME; LANDSCAPE; EVOLUTION; IMPACT;

D O I：

10.1126/science.aao3791

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Although genomic instability, epigenetic abnormality, and gene expression dysregulation are hallmarks of colorectal cancer, these features have not been simultaneously analyzed at single-cell resolution. Using optimized single-cell multiomics sequencing together with multiregional sampling of the primary tumor and lymphatic and distant metastases, we developed insights beyond intratumoral heterogeneity. Genome-wide DNA methylation levels were relatively consistent within a single genetic sublineage. The genome-wide DNA demethylation patterns of cancer cells were consistent in all 10 patients whose DNA we sequenced. The cancer cells' DNA demethylation degrees clearly correlated with the densities of the heterochromatin-associated histone modification H3K9me3 of normal tissue and those of repetitive element long interspersed nuclear element 1. Our work demonstrates the feasibility of reconstructing genetic lineages and tracing their epigenomic and transcriptomic dynamics with single-cell multiomics sequencing.

引用

页码：1060 / +

页数：43

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