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

ABSTRACT: in vitro in various cell types and in vivo in placentae and blood Smchd1 removal results in loss of imprinting at the PWS cluster on mouse chromosome 7. 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.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE329973 | GEO | 2026/08/30

REPOSITORIES: GEO

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

Project description:in vitro in various cell types and in vivo in placentae and blood Smchd1 removal results in loss of imprinting at the PWS cluster on mouse chromosome 7. Our aim was to assess whether CNS specific Smchd1 deletion after early development in vivo likewise resulted in activation of maternal PWS cluster genes - specifically the small nucleolar RNAs (snoRNAs) and long non-coding RNAs (lncRNAs) in the region, and what effects this deletion may have genome-wide. We found significant maternal gene activation at imprinted genes across the locus including snoRNAs and importantly activation of a lncRNA responsible for reciprocal imprinting on the paternal allele did not affect the imprinting status of paternally imprinted gene Ube3a. We also observed minimal genome-wide changes.

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