Human methylome studies across different cell types have been essential for understanding cell-type-specific methylation patterns and gene regulation. Loyfer et al. performed deep whole-genome bisulfite sequencing at an average depth of 30× on 39 human cell-type groups sorted from 205 healthy tissue samples. These methylomes showed large similarities between replicates of the same cell type, which suggests that cell-type-specific programs rather than environmental factors are the main determinants of DNA methylation. The authors identified methylation blocks of CpG sites that reflect human developmental lineage of cell types. They also characterized cell-type-specific unmethylated genomic regions and identified the top 250 unmethylated markers for each cell type. Fragment-level analysis led to the identification of cell-type-specific enhancer regions and regulatory transcription factors. Cell-type-specific hypermethylated regions were found to be enriched for CpG islands, Polycomb targets and CTCF binding sites. Using the atlas, interestingly, the authors detected a high concentration of endothelial-cell-derived cell-free DNA in patients with COVID-19. The study provides a valuable human methylome atlas of normal cell types, as well as cell-type-specific biomarkers with potential clinical applications.

Original reference: Nature 613, 355–364 (2023)