Single-Cell Genomics and Epigenomics

Abstract

The cell is the fundamental unit of life, in which the blueprint of the genome is transcribed and translated into biological function. Most of our current understanding of the genome, epigenome, and transcriptome is based on analysis of millions of cells as a bulk population. These analyses are highly informative but they do not provide information about the heterogeneity and molecular dynamics that occur within a population of cells, nor any information about an underrepresented cell subpopulation that could have a differential or crucial function in a specific biological context. Thus, single cell analysis is, without doubt, an invaluable approach to understand fundamental biology in embryonic development, normal organs, and disease. Improvements in techniques for the isolation of single cells, whole genome or transcriptome amplification, and genome-wide analysis platforms have allowed high-resolution analysis of the genome and transcriptome, and also have potential to reveal the epigenome map of one cell. In particular, the rapid advances in next-generation sequencing technologies are raising new methodologies in these areas allowing sequencing of the small amounts of DNA and RNA present in single cells. The integration of the knowledge from different types of single cell "omics" datasets will revolutionize the way we understand whole-organism science and will have high impact on both basic biological research and medicine. For example, a combination of single-cell "omics" datasets will be applied to reveal important biological insights, such as: a detailed cell lineage tree in higher organisms; a deep understanding of embryonic development from one single cell onwards; and a dissection of tumor heterogeneity. Integration of genomics and transcriptomics in single cancer cells will also provide valuable information about the functional consequences of mutations and copy number variations in these cells. In this chapter, we first review the major technological developments achieved in single cell "omics" as well as the technical challenges to overcome and the potential of future developments. We then describe the impact that these methods would have on normal development and disease and their potential applications. Finally, we discuss our vision of the future developments and breakthroughs of single cell "omics" with a special focus on the integration of all these methods to understand whole-organism biology.