Hepatocyte polyploidization during ageing protects against transcriptional dysregulation and chronic liver disease

Single-nucleus RNA-seq2 method allows deep transcriptomic characterization of nuclei isolated from frozen archived tissues. We have used this approach to study the transcriptional profile of individual hepatocytes with different levels of ploidy in young and old wild-type, as well as three other haploinsufficient Mus musculus mice strains. Our data suggest that polyploidisation, a hallmark of ageing in hepatocytes, is also a mechanism by which tetraploid cells are able to buffer genomic perturbations during ageing via non-random allelic segregation of the wild type allele.