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.

在哺乳动物基因组中，一部分基因受到基因组印记的调节，导致一个亲本等位基因的沉默。印记对于大脑皮层的发育至关重要，但对单个细胞的普遍性和功能影响尚不清楚。在这里，我们确定了皮质细胞类型中的等位基因表达，并建立了一个定量平台来询问单细胞中的印记。我们创建了具有单亲染色体二体性（UPD）的细胞，其中包含母本或父本染色体的两个拷贝；因此，印记基因将被过表达两倍或不表达。通过 UPD 的基因标记，我们以前所未有的单细胞分辨率确定了细胞表型和对印记基因表达失调的转录反应。我们发现了意想不到的细胞类型特异性和印记在调节皮质星形胶质细胞存活中的新功能。更一般地说，我们的结果表明神经胶质星形胶质细胞谱系中印记基因表达的功能相关性，从而产生皮质细胞类型多样性。