Single-Cell DNA Methylation Profiling: Technologies and Biological Applications

DNA methylation is an epigenetic modification that plays an important role in gene expression regulation, development, and disease. Recent technological innovations have spurred the development of methods that enable us to study the occurrence and biology of this mark at the single-cell level. Apart from answering fundamental biological questions about heterogeneous systems or rare cell types, low-input methods also bring clinical applications within reach. Ultimately, integrating these data with other single-cell data sets will allow deciphering multiple layers of gene expression regulation within each individual cell. Here, we review the approaches that have been developed to facilitate single-cell DNA methylation profiling, their biological applications, and how these will further our understanding of the biology of DNA methylation.