title: Biased allelic expression in human primary fibroblast single cells.
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.
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Christelle
authors.initials: C
authors.lastname: Borel
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland; Institute of Genetics and Genomics of Geneva, 1211 Geneva, Switzerland; Swiss Institute of Bioinformatics, 1211 Geneva, Switzerland.
authors.forename: Pedro G
authors.initials: PG
authors.lastname: Ferreira
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Federico
authors.initials: F
authors.lastname: Santoni
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland; Institute of Genetics and Genomics of Geneva, 1211 Geneva, Switzerland; Swiss Institute of Bioinformatics, 1211 Geneva, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Delaneau
authors.affiliation: Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Fort
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Konstantin Y
authors.initials: KY
authors.lastname: Popadin
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Garieri
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Emilie
authors.initials: E
authors.lastname: Falconnet
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Pascale
authors.initials: P
authors.lastname: Ribaux
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland; Service of Genetic Medicine, University Hospitals of Geneva, 1211 Geneva, Switzerland.
authors.forename: Michel
authors.initials: M
authors.lastname: Guipponi
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland.
authors.forename: Ismael
authors.initials: I
authors.lastname: Padioleau
authors.affiliation: Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Piero
authors.initials: P
authors.lastname: Carninci
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland; Institute of Genetics and Genomics of Geneva, 1211 Geneva, Switzerland; Swiss Institute of Bioinformatics, 1211 Geneva, Switzerland; Center of Excellence for Genomic Medicine Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Biomedical Research Foundation Academy of Athens, Athens 11527, Greece. Electronic address: emmanouil.dermitzakis@unige.ch.
authors.forename: Emmanouil T
authors.initials: ET
authors.lastname: Dermitzakis
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva, 1211 Geneva, Switzerland; Institute of Genetics and Genomics of Geneva, 1211 Geneva, Switzerland; Service of Genetic Medicine, University Hospitals of Geneva, 1211 Geneva, Switzerland. Electronic address: stylianos.antonarakis@unige.ch.
authors.forename: Stylianos E
authors.initials: SE
authors.lastname: Antonarakis
mesh_terms: D000483:Alleles; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology*; D015894:Genome, Human; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017423:Sequence Analysis, RNA; D059010:Single-Cell Analysis
chemical_list: D018076:DNA, Complementary; D012333:RNA, Messenger