Abstract
Over the past decade, genomic analyses of single cells-the fundamental units of life-have become possible. Single-cell DNA sequencing has shed light on biological questions that were previously inaccessible across diverse fields of research, including somatic mutagenesis, organismal development, genome function, and microbiology. Single-cell DNA sequencing also promises significant future biomedical and clinical impact, spanning oncology, fertility, and beyond. While single-cell approaches that profile RNA and protein have greatly expanded our understanding of cellular diversity, many fundamental questions in biology and important biomedical applications require analysis of the DNA of single cells. Here, we review the applications and biological questions for which single-cell DNA sequencing is uniquely suited or required. We include a discussion of the fields that will be impacted by single-cell DNA sequencing as the technology continues to advance.
Highlights
Single-cell DNA sequencing encompasses a suite of technologies and approaches that interrogate DNA at the level of single cells
Much like the voice of a single individual or a small number of individuals can be drowned out in a large crowd, genomic signals that are present in only one or a small number of cells in a sample may be undetectable without interrogating single-cell genomes
The development of scDNA-seq methods has at every step been motivated by biological questions that seek to explore the cellular genomic diversity that would otherwise be missed by bulk sequencing
Summary
Single-cell DNA sequencing (scDNA-seq) encompasses a suite of technologies and approaches that interrogate DNA at the level of single cells. These technologies contrast with standard DNA sequencing, known as bulk sequencing, which homogenizes the DNA content of usually thousands to millions of cells. We discuss the major biological fields that scDNA-seq has impacted and the discoveries it has enabled. These include a wide array of fields: somatic mutation and mosaicism, organismal development, germ cell mutation and development, fertility, cancer, epigenetic regulation of the genome, genome organization, and microbiology. While single-cell genomics is sometimes used in the literature to refer to single-cell RNA sequencing (scRNA-seq), to avoid terminological confusion, here, single-cell genomics and single-cell transcriptomics refer to scDNA-seq and scRNA-seq, respectively
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