Extended Data Fig. 8: Enrichment of bystander modifications in mesenchymal stromal cells.
a,b) Transcriptomic changes upon epigenetic editing in MSCs was analyzed for two of the three donors in independent experiments. a) The scatter-plot depicts reads-per million (RPM) in control versus experiment. b) Comparison of DNAm changes (n = 3) and transcriptomic changes (n = 2) revealed no clear association between DNAm changes and gene expression changes. c,d) In our previous work, we have identified 646 CpGs that gain and 2442 CpGs that lose DNAm during culture expansion of MSCs41. Since these CpGs may be associated with replicative senescence, they are referred to as senescence-hyper and senescence-hypo, respectively. We have analyzed if these CpGs are enriched in bystander modifications upon epigenetic editing at age-hypermethylated sites in MSCs. a) Gaussian kernel density estimate and b) cumulative distribution function demonstrates that bystander effects are slightly enriched in senescence-hyper (P < 10−06) and senescence-hypo-CpGs (P < 10−9, two-sided, two-sample Kolmogorov–Smirnov-test). e,f) Gaussian kernel density estimate and cumulative distribution function comparing the entirety of CpGs from the BeadChip with age-associated CpGs in blood. Bystander effects are significantly enriched at age-hypermethylated sites (P < 10−15, two-sided, two-sample Kolmogorov–Smirnov-test). g,h) Density plots of gaussian kernel density estimate of bystanders at CpGs that gain or lose DNAm with aging in T cells, corresponding to Fig. 6c, d.
