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Single-Cell RNA-Seq Reveals Dynamic, Random Monoallelic Gene Expression in Mammalian Cells

Science  10 Jan 2014:
Vol. 343, Issue 6167, pp. 193-196
DOI: 10.1126/science.1245316

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Expressing One Allele at a Time

Although genetic traits are often dominant or recessive, the impact of the same heterozygous genotype can vary quite a bit between individuals. Deng et al. (p. 193), analyzed global gene expression in hundreds of individual mouse cells and found that a substantial fraction of the genes only expressed one of the alleles, chosen randomly, at any given point in time. Such stochasticity in transcription increases the heterogeneity among cells and likely contributes to the phenotypic variance among individuals of identical genotype.

Abstract

Expression from both alleles is generally observed in analyses of diploid cell populations, but studies addressing allelic expression patterns genome-wide in single cells are lacking. Here, we present global analyses of allelic expression across individual cells of mouse preimplantation embryos of mixed background (CAST/EiJ × C57BL/6J). We discovered abundant (12 to 24%) monoallelic expression of autosomal genes and that expression of the two alleles occurs independently. The monoallelic expression appeared random and dynamic because there was considerable variation among closely related embryonic cells. Similar patterns of monoallelic expression were observed in mature cells. Our allelic expression analysis also demonstrates the de novo inactivation of the paternal X chromosome. We conclude that independent and stochastic allelic transcription generates abundant random monoallelic expression in the mammalian cell.

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