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Scientific article
English

Biased allelic expression in human primary fibroblast single cells

Published inAmerican journal of human genetics, vol. 96, no. 1, p. 70-80
Publication date2015
Abstract

The study of gene expression in mammalian single cells via genomic technologies now provides the possibility to investigate the patterns of allelic gene expression. We used single-cell RNA sequencing to detect the allele-specific mRNA level in 203 single human primary fibroblasts over 133,633 unique heterozygous single-nucleotide variants (hetSNVs). We observed that at the snapshot of analyses, each cell contained mostly transcripts from one allele from the majority of genes; indeed, 76.4% of the hetSNVs displayed stochastic monoallelic expression in single cells. Remarkably, adjacent hetSNVs exhibited a haplotype-consistent allelic ratio; in contrast, distant sites located in two different genes were independent of the haplotype structure. Moreover, the allele-specific expression in single cells correlated with the abundance of the cellular transcript. We observed that genes expressing both alleles in the majority of the single cells at a given time point were rare and enriched with highly expressed genes. The relative abundance of each allele in a cell was controlled by some regulatory mechanisms given that we observed related single-cell allelic profiles according to genes. Overall, these results have direct implications in cellular phenotypic variability.

Keywords
  • Alleles
  • DNA, Complementary/genetics/metabolism
  • Fibroblasts/cytology
  • Genome, Human
  • Haplotypes
  • Heterozygote
  • Humans
  • Phenotype
  • RNA, Messenger/genetics/metabolism
  • Sequence Analysis, RNA
  • Single-Cell Analysis
Citation (ISO format)
BOREL, Christelle et al. Biased allelic expression in human primary fibroblast single cells. In: American journal of human genetics, 2015, vol. 96, n° 1, p. 70–80. doi: 10.1016/j.ajhg.2014.12.001
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Article (Published version)
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ISSN of the journal0002-9297
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