February 23, 2016, cell research (Cell Research) magazine online published has Peking University life science College biological dynamic optical imaging Center soup rich paid research group, and huangyan friends research group and capital Medical University subsidiary Beijing century altar hospital cum Peking University Nineth clinical medical school Hepatobiliary pancreatic surgical Peng Jirun research group cooperation of latest research results--unicellular three restructuring learn measuring sequence reveals liver cancer cell gene group, and table views Group and transcription group of different quality sex (Single-cell triple omics sequencing reveals genetic, epigenetic, and transcriptomic heterogeneity in hepatocellular carcinomas)。The study establishes a new restructuring of the single cell three sequencing methods (scTrio-seq), implemented for the first time from the same single cell of three kinds of groups of high-throughput sequencing information obtained and levels of liver cancer cells from a single cell in three existing closely related to the high degree of heterogeneity.

Organisms with an organization or between cells of the same cell type, and often there is a big difference.While traditional group learning based on hybrid cells research failed to observe differences between cells, and can cause part of key cell characteristics are glossed over.Single cell Genomics analysis technique of systematic and in-depth study of specific types of cells characteristics and the differences between cells play an important role.In recent years, scientists have been in the genome, transcriptome and groups such as DNA methylation levels a single cell of a single set of high-throughput sequencing analysis and research on a single germ cell, early embryonic cells and group characteristics of the cancer cells.

Single cell genomics research has always been the dream for scientists.Recently, the international research group on reporting the single pair of genomics and sequencing technology (single cell genome and transcriptome;Unicellular group of DNA methylation and transcription), however, nobody has been able to breakthrough single three or more groups of parallel sequencing technology bottleneck.

ScTrio-seq technology for the first time to achieve a high-throughput sequencing analysis of single cell three restructuring, to simultaneously detect mammals within the same single cell genome, DNA methylation and the transcriptome information.

Single cell three recombinant learning sequencing technology（scTrio-seq）

Corresponding relation between three groups in a single cell

Two subpopulations of cells in a cancer DNA copy number differences

The study found that in a single cell, DNA methylation in gene region and has a very strong positive correlation between gene expression and methylation in different regions may have different effects on gene expression.Then, researchers also found that the genome of DNA copy number and the range of gene expression also has a strong positive correlation between DNA copy number areas, its gene expression was also increased, and vice versa, at the single cell level proved gene dosage effect.However DNA copy number variation and does not affect its DNA methylation changes.

China is a high incidence of liver cancer, and liver cancer patients with a poor prognosis and mechanism study on the occurrence and metastasis of liver cancer is around the corner.And cancer organizations is one in the genome, transcriptome and apparent set of levels are highly heterogeneous cell populations, so needed by single cell analysis techniques to study three groups of tumor control mechanism between three groups.

The team uses the latest scTrio-seq technology developed to one of the 25 patients with hepatocellular carcinoma cells carried out three simultaneous analysis of omics.Three sets of data show that 25 of liver cancer cells from two different cell subpopulations.On this basis, researchers analyzed two subsets of difference in the three groups.Studies have found that at the genomic level, subsets of I cells contain more increased copy number of chromosomes and chromosome segments, and subgroup II contains more copy number reduction in the chromosomes and chromosome segments;In the DNA methylation level, Asian Group I group II the Republic of Namibia has higher levels of DNA methylation, and produces most of the difference in CpG Islands (CGI) region;At the transcriptional level, a number of genes related to immune response and inflammation, as well as complement activation related genes expressed in subsets of I have significantly reduced, with cancer and metastasis-related gene ANO1 expression and S100A11, there are also significant differences in the two subsets.Multiple groups of data display, in the detection of hepatocellular carcinoma cells, on a number of smaller subsets I cells have more DNA copy number variation and higher levels of DNA methylation, may be more susceptible to escape the immune system of patients with recognition and may be more prone to transfer.

College of life sciences, Peking University Center for bio-optical imaging soup rich pay researcher, Huang Yan yi researcher and the Beijing shijitan Hospital of Hepatobiliary and pancreatic surgery Professor Peng Jirun is the co-author of the paper.Doctoral School of life sciences, Peking University Hou Yu and master Guo Huahu of the Medical Department of Peking University was tied for the authors of this paper.Fuchou researcher and Huang Yan yi is also a researcher at Peking University and Tsinghua University's Center for life sciences.The study supported by the National Natural Science Foundation and the Department of science and technology.