Dissection of Cancer Heterogeneity by Single Cell Sequencing

Cancer is one leading cause of death worldwide. Major hurdles of efficacious cancer therapy stem from its intrinsic molecular and cellular heterogeneity. The emerging single cell sequencing technology have already shed light upon the fundamental pathology of caner and could provide clinical promises with crucial subpopulation information. In contrast to bulk sequencing methods which do not take intercellular heterogeneity into account, single cell sequencing can capture the genetic and epigenetic changes between cells originating from the same tumor, in hope of understanding the underlying carcinogenic mechanisms with a lot more dimensions. In this review, we first describe the heterogeneous characteristics of cancer, including the concept of cancer stem cells. Then we outline modern single cell sequencing techniques at different molecular scales, from the genome to epigenome, and perhaps higher chromatin structures. Their uses and drawbacks in the basic cancer research and clinical application are discussed. We also proposed that other basic research topics or novel biotechnologies, including cancer organoids, 3D printing, and gut microbiome, are possible to be combined with the current single cell sequencing approach for broader research and clinical applications.