New Method for Detailed DNA Methylation Analysis in Individual Cells

Scientists at the Van Andel Institute have introduced a new method for analyzing DNA methylation in individual cells. The technique, called scDEEP-mC, enables high-resolution mapping of methylation patterns across the genome, enhancing the ability to detect subtle and cell-specific epigenetic features.

DNA methylation is a chemical modification that helps regulate gene expression and cell identity without altering the DNA sequence itself. It plays a critical role in development, cell differentiation and genomic stability. Aberrant methylation patterns have been linked to a range of diseases, including cancer.

Until now, techniques for assessing methylation in single cells have lacked the resolution and efficiency required for broad application. scDEEP-mC addresses these limitations by generating comprehensive methylation maps of DNA methylation that allow researchers to identify distinct cell types and trace developmental changes at the individual cell level. The method also allows for comparisons between newly replicated and older cells, which could provide insights into aging and disease progression.

The study, published in Nature Communications, describes how scDEEP-mC supports several advanced analyses in single cells. These include the estimating of cellular age using epigenetic clocks, analysis of hemimethylation and creation of whole-chromosome X-inactivation epigenetic profiles.

The improved resolution allows researchers to study methylation dynamics during DNA replication, a process that was previously difficult to observe at the single-cell level.

Previous single-cell methylation methods relied on pooled data from multiple cells, which obscured cell-specific differences. Such averaging techniques limited the ability to identify rare cell types or detect nuanced epigenetic variations. In contrast, scDEEP-mC generates detailed individual cell profiles, revealing differences that would otherwise remain hidden.

The method's efficiency and depth of coverage position it as a valuable tool for studying complex tissues, where understanding individual cell behavior is essential for unraveling disease mechanisms.

Reference: Spix NJ, Habib WA, Zhang Z, et al. High-coverage allele-resolved single-cell DNA methylation profiling reveals cell lineage, X-inactivation state, and replication dynamics. Nat Commun. 2025;16(1):6273. doi: 10.1038/s41467-025-61589-1

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According to the source: Technology Networks.