Advances in single-cell epigenomics of the immune system

Abstract Single-cell epigenomics has recently emerged as a group of powerful technologies by which different layers of epigenetic regulation can be studied on the single-cell level and hence allow for unbiased investigation of cell identity and function. Especially by integrating multiple components of the epigenome into multiomics measurements, cellular heterogeneity as well as the molecular mechanisms connecting the genome and its functional output can be explored with unprecedented resolution. Combined with very recent techniques which allow cell lineage tracing based on somatic mutations in humans, this multilayered information will provide insights into a cell's history and its future potential in normal development, physiology, and disease. Here, we review the evolution of single-cell epigenomic techniques over the last decade, discuss analytical challenges and solutions of this novel data type, and present a selection of paradigmatic findings achieved by single-cell epigenomics with particular focus on the immune system.