Effect of Smchd1 deletion via Nestin-Cre in mouse brain tissue I

Our aim was to assess whether CNS specific Smchd1 deletion after early development in vivo likewise resulted in activation of maternal PWS cluster genes, and what effects this deletion may have genome-wide. We found significant maternal gene activation at imprinted genes across the locus in both hypothalamus and cortex and minimal genome-wide changes.

We further wanted to understand if this gene activation upon removal of SMCHD1 held true in humans so we depleted SMCHD1 in neural progenitor cells differentiated from PWS patient-derived iPSCs and compared gene expression between SMCHD1 depleted and control cells. We found that removal of SMCHD1 likewise causes maternal PWS gene activation in a human context, albeit variably with ASO depletion, also with minimal genome-wide effects.