Single-cell epigenomic analysis of premature aging syndromes.
DNA damage has been found affecting most of the aging phenotypes. Recently using the single-cell whole-genome sequencing method that we developed, we have found DNA mutations, which is a result of errors in DNA repair, accumulate significantly during aging in humans. Epigenetic alterations were also shown recently to be a result of DNA damage. However, only progressive epigenetic changes have been studied, e.g., DNA methylation clock, and little is known about heterogeneous epigenetic changes, which vary cell-to-cell and are more likely direct consequences of DNA damage. Such cell-to-cell variation requires a single-cell/clone analysis to analyze. Here, we will focus on DNA methylation. Using single-cell bisulfite sequencing, we will test if heterogeneous DNA methylation changes, called “epimutations”, accumulate during DNA damage and aging.