Cell-Type Specificity of Genomic Imprinting in Cerebral Cortex.

In mammalian genomes, a subset of genes is regulated by genomic imprinting, resulting in silencing of one parental allele. Imprinting is essential for cerebral cortex development, but prevalence and functional impact in individual cells is unclear. Here, we determined allelic expression in cortical cell types and established a quantitative platform to interrogate imprinting in single cells. We created cells with uniparental chromosome disomy (UPD) containing two copies of either the maternal or the paternal chromosome; hence, imprinted genes will be 2-fold overexpressed or not expressed. By genetic labeling of UPD, we determined cellular phenotypes and transcriptional responses to deregulated imprinted gene expression at unprecedented single-cell resolution. We discovered an unexpected degree of cell-type specificity and a novel function of imprinting in the regulation of cortical astrocyte survival. More generally, our results suggest functional relevance of imprinted gene expression in glial astrocyte lineage and thus for generating cortical cell-type diversity. • Uniform allelic expression of imprinted genes in major forebrain cell types • Cortical cell-type-specific expression levels of imprinted genes • Cell-type-specific transcriptional responses in uniparental chromosome disomy (UPD) • Cortical cell-type-specific phenotype in cells with UPD Laukoter et al. analyze prevalence and functional impact of genomic imprinting, an epigenetic phenomenon resulting in the silencing of one parental allele, in cerebral cortex development at the single-cell level. They find a high degree of cell-type specificity and a novel function of imprinting in cortical astrocyte development. [ABSTRACT FROM AUTHOR]