Clonal tracing with somatic epimutations reveals dynamics of blood ageing.

ABSTRACT: Current approaches used to track stem cell clones through differentiation require genetic engineering^1,2 or rely on sparse somatic DNA variants^3,4, which limits their wide application. Here we discover that DNA methylation of a subset of CpG sites reflects cellular differentiation, whereas another subset undergoes stochastic epimutations and can serve as digital barcodes of clonal identity. We demonstrate that targeted single-cell profiling of DNA methylation⁵ at single-CpG resolution can accurately extract both layers of information. To that end, we develop EPI-Clone, a method for transgene-free lineage tracing at scale. Applied to mouse and human haematopoiesis, we capture hundreds of clonal differentiation trajectories across tens of individuals and 230,

SUBMITTER: Scherer M 

PROVIDER: S-EPMC12240852 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature