Single-cell Multi-omics Sequencing and Analyses of Human Colorectal Cancer

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 multi-omics sequencing together with multi-regional sampling of the primary tumor, lymphatic and distant metastases, we provide insights beyond intratumoral heterogeneity. Genome-wide DNA methylation levels were relatively consistent within a single genetic sub-lineage. The genome-wide DNA demethylation patterns of cancer cells were consistent in all 10 sequenced patients. Our work demonstrates the feasibility of reconstructing genetic lineages, and tracing their epigenomic and transcriptomic dynamics with single-cell multi-omics sequencing. Overall design: Single cell RNA-seq and Bisulfite-seq on whole cells or by TrioSeq2. [scTrioSeq2Rna and scTrioSeq2Met Samples] Sample Title structure: Library_PatientID_SamplingPositions_CellID SamplingPositions abbreviations: PT: Primary Tumor LN: Lymph Node metastasis ML: Liver Metastasis MP: Post-treatment Liver Metastasis

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Bian S, Hou Y, Zhou X, Li X, Yong J, Wang Y, Wang W, Yan J, Hu B, Guo H, Wang J, Gao S, Mao Y, Dong J, Zhu P, Xiu D, Yan L, Wen L, Qiao J, Tang F, Fu W