Stochastic Choice of Allelic Expression in Human Neural Stem Cells
Stochastic Choice of Allelic Expression in Human Neural Stem Cells
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DOI：
10.1002/stem.1155
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发表时间：
2012-09-01
期刊：
影响因子：
5.2
通讯作者：
Price, Jack
中科院分区：
文献类型：
--
作者：
Jeffries, Aaron R.;Perfect, Leo W.;Price, Jack
单等位基因基因表达，如基因组印记，是很好的描述。不太清楚的是经历随机单等位基因表达（MA）的基因，其中特定的细胞克隆在给定的基因座上仅表达一个等位基因。我们对来自大脑皮层、纹状体和脊髓的人克隆神经干细胞进行了全基因组等位基因表达评估，每个细胞具有不同的基因型。我们分析了三个独立的克隆线从每个捐助者，区分随机MA基因型效应。大约2%的基因显示常染色体MA的证据，在其中约一半，等位基因的表达是随机的不同克隆之间。这些基因座中有许多是已知的神经发育基因，如OTX 2和OLIG 2。与低甲基化双等位基因位点相比，单等位基因基因也显示出DNA甲基化水平增加。已鉴定的单等位基因位点在胎儿脑中显示改变的染色质特征，表明这种现象在体内相关。我们的结论是，随机等位基因表达是普遍的神经干细胞，提供克隆多样性的发展组织，如人脑。干细胞2012;30：1938-1947
Monoallelic gene expression, such as genomic imprinting, is well described. Less well-characterized are genes undergoing stochastic monoallelic expression (MA), where specific clones of cells express just one allele at a given locus. We performed genome-wide allelic expression assessment of human clonal neural stem cells derived from cerebral cortex, striatum, and spinal cord, each with differing genotypes. We assayed three separate clonal lines from each donor, distinguishing stochastic MA from genotypic effects. Roughly 2% of genes showed evidence for autosomal MA, and in about half of these, allelic expression was stochastic between different clones. Many of these loci were known neurodevelopmental genes, such as OTX2 and OLIG2. Monoallelic genes also showed increased levels of DNA methylation compared to hypomethylated biallelic loci. Identified monoallelic gene loci showed altered chromatin signatures in fetal brain, suggesting an in vivo correlate of this phenomenon. We conclude that stochastic allelic expression is prevalent in neural stem cells, providing clonal diversity to developing tissues such as the human brain. STEM CELLS 2012;30:1938-1947