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Stochastic Choice of Allelic Expression in Human Neural Stem Cells

Jeffries, Aaron R and Perfect, Leo W and Ledderose, Julia and Schalkwyk, Leonard C and Bray, Nicholas J and Mill, Jonathan and Price, Jack (2012) 'Stochastic Choice of Allelic Expression in Human Neural Stem Cells.' Stem Cells, 30 (9). pp. 1938-1947. ISSN 1066-5099

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<jats:title>Abstract</jats:title> <jats:p>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.</jats:p>

Item Type: Article
Uncontrolled Keywords: Neural stem cells; Epigenomics; Allelic imbalance; Monoallelic expression; DNA methylation; Brain
Subjects: Q Science > QH Natural history > QH426 Genetics
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 11 Nov 2014 10:11
Last Modified: 18 Jan 2022 18:33

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