During life-time, adult stem cells accumulate epigenetic alterations that lead to the appearance and expansion of mutant stem cell clones. These cells lead to tissue dysfunction and cancer. Our group is interested to understand the molecular mechanisms driving the fixation of these mutant clones and tumorigenesis. By employing cutting-edge technologies including single-cell genome-wide experiments, we analyse primary cells and tissues to mechanistically dissect the origin and to understand the function of these epigenetic alterations, mainly focusing on DNA methylation. (Figure adapted from Ermolaeva, M., Neri, F., et al., Nature Reviews MCB, 2018.