Single Cell triple omics sequencing reveals genetic and epigenetic heterogeneity in hepatocellular carcinoma

Single cell genome, DNA methylome, and transcriptome sequencing has been achieved separately. However, to analyze the regulation of RNA expression by genetic and epigenetic factors within an individual cell, it is necessary to analyze these omics simultaneously from the same single cell. Here we developed a single cell triple omics sequencing technique- scTrio-seq, to analyze the genome, DNA methylome, and transcriptome concurrently of a mammalian cell. Overall design: 6 single human HepG2 cell line cells were sequenced using the newly developed scTrio-seq, other 2 HepG2 cells were sequenced using scRNA-seq and other 2 HepG2 cells were sequenced using scRRBS as technique control. 6 single mouse embryonic stem cells (mESCs) were sequenced using the newly developted scTrio-seq. Meanwhile, two scRNA-seq and two scRRBS were also completed using two mESCs separately. 26 single cells from hepatocellular carcinoma were sequenced using scTrio-seq to analyze the regulation relations between three omics of cancer cells.