Single-cell multiomics sequencing and analyses of human colorectal cancer.
Shuhui Bian, Yu Hou, Xin Zhou, Xianlong Li, Jun Yong, Yicheng Wang, Wendong Wang, Jia Yan, Boqiang Hu, Hongshan Guo, Jilian Wang, Shuai Gao, Yunuo Mao, Ji Dong, Ping Zhu, Dianrong Xiu, Liying Yan, Lu Wen, Jie Qiao, Fuchou Tang, Wei Fu
Author Information
Shuhui Bian: Beijing Advanced Innovation Center for Genomics, College of Life Sciences, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100871, China. ORCID
Yu Hou: Beijing Advanced Innovation Center for Genomics, College of Life Sciences, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100871, China. ORCID
Xin Zhou: Department of General Surgery, Peking University Third Hospital, Beijing 100191, China. ORCID
Xianlong Li: Beijing Advanced Innovation Center for Genomics, College of Life Sciences, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100871, China. ORCID
Jun Yong: Beijing Advanced Innovation Center for Genomics, College of Life Sciences, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100871, China. ORCID
Yicheng Wang: Beijing Advanced Innovation Center for Genomics, College of Life Sciences, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100871, China. ORCID
Wendong Wang: Department of General Surgery, Peking University Third Hospital, Beijing 100191, China. ORCID
Jia Yan: Beijing Advanced Innovation Center for Genomics, College of Life Sciences, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100871, China. ORCID
Boqiang Hu: Beijing Advanced Innovation Center for Genomics, College of Life Sciences, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100871, China. ORCID
Hongshan Guo: Beijing Advanced Innovation Center for Genomics, College of Life Sciences, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100871, China. ORCID
Jilian Wang: Department of General Surgery, Peking University Third Hospital, Beijing 100191, China. ORCID
Shuai Gao: Beijing Advanced Innovation Center for Genomics, College of Life Sciences, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100871, China. ORCID
Yunuo Mao: Beijing Advanced Innovation Center for Genomics, College of Life Sciences, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100871, China. ORCID
Ji Dong: Beijing Advanced Innovation Center for Genomics, College of Life Sciences, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100871, China.
Ping Zhu: Beijing Advanced Innovation Center for Genomics, College of Life Sciences, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100871, China.
Dianrong Xiu: Department of General Surgery, Peking University Third Hospital, Beijing 100191, China.
Liying Yan: Beijing Advanced Innovation Center for Genomics, College of Life Sciences, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100871, China. ORCID
Lu Wen: Beijing Advanced Innovation Center for Genomics, College of Life Sciences, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100871, China.
Jie Qiao: Beijing Advanced Innovation Center for Genomics, College of Life Sciences, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100871, China. jie.qiao@263.net tangfuchou@pku.edu.cn fuwei@bjmu.edu.cn. ORCID
Fuchou Tang: Beijing Advanced Innovation Center for Genomics, College of Life Sciences, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100871, China. jie.qiao@263.net tangfuchou@pku.edu.cn fuwei@bjmu.edu.cn. ORCID
Wei Fu: Department of General Surgery, Peking University Third Hospital, Beijing 100191, China. jie.qiao@263.net tangfuchou@pku.edu.cn fuwei@bjmu.edu.cn. ORCID
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.
