Stochastic Choice of Allelic Expression in Human Neural Stem Cells123. (20th August 2012)

• Record Type: Journal Article
• Authors: Jeffries, Aaron R.; Perfect, Leo W.; Ledderose, Julia; Schalkwyk, Leonard C.; Bray, Nicholas J.; Mill, Jonathan; Price, Jack
• Is Part Of: Stem cells. Volume 30:Number 9(2012)
• Page Start: 1938
• Page End: 1947
• Publication Date: 2012-08-20
• Subjects: Neural stem cells -- Epigenomics -- Allelic imbalance -- Monoallelic expression -- DNA methylation -- Brain; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.1155
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract: 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