Lei Zhang, PhD

Single-cell epigenomic analysis of premature aging syndromes

DNA damage affects most of the aging phenotypes. Using the single-cell whole-genome sequencing method that Dr. Zhang and her colleagues developed, they recently have found DNA mutations, results of DNA repair errors, accumulate significantly during aging in humans. Epigenetic alterations were also shown 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 stochastic 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. Dr. Zhang’s team will focus on DNA methylation. Using single-cell bisulfite sequencing, they will test if stochastic DNA methylation changes, called “epimutations”, accumulate during aging and pre-mature aging syndromes in humans and mice. The proposed research hopes to provide strong evidence if epigenome instability is a result of DNA damage and progress during aging.