Shared molecular consequences of epigenetic machinery disruption in neuronal progenitors [neurodevelopmental_dataset]

Phenotypically KO of either model led to premature differentiation, so we systematically catalogued changes during differentiation in our model in an effort to be able to differentiate changes secondary to altered differentiation rates. Upon KO of 46 EM genes, DNA methyltransferases showed the biggest change in DNAm with other genes showing subtle changes. We do observe a single shared DMR (Zic4) within the entire cohort.

Finally, we observe 1074 haplotype-specific (imprinted and non-imprinted) DMRs, notably a large number of these show corresponding genetic variation within the DMR. Our findings highlight the promise of combined ONT and RNA sequencing as a useful strategy for understanding epigenetic and transcriptomic abnormalities in disease-relevant cells across diverse MDEM contexts.