Single cell transcriptome in aneuploidies reveals mechanisms of gene dosage imbalance.

Details

Serval ID
serval:BIB_1AC470E44968
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Single cell transcriptome in aneuploidies reveals mechanisms of gene dosage imbalance.
Journal
Nature communications
Author(s)
Stamoulis G., Garieri M., Makrythanasis P., Letourneau A., Guipponi M., Panousis N., Sloan-Béna F., Falconnet E., Ribaux P., Borel C., Santoni F., Antonarakis S.E.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
03/10/2019
Peer-reviewed
Oui
Volume
10
Number
1
Pages
4495
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
Publication Status: epublish
Abstract
Aneuploidy is a major source of gene dosage imbalance due to copy number alterations (CNA), and viable human trisomies are model disorders of altered gene expression. We study gene and allele-specific expression (ASE) of 9668 single-cell fibroblasts from trisomy 21 (T21) discordant twins and from mosaic T21, T18, T13 and T8. We examine 928 single cells with deep scRNAseq. Expected and observed overexpression of trisomic genes in trisomic vs. diploid bulk RNAseq is not detectable in trisomic vs. diploid single cells. Instead, for trisomic genes with low-to-average expression, their altered gene dosage is mainly due to the higher fraction of trisomic cells simultaneously expressing these genes, in agreement with a stochastic 2-state burst-like model of transcription. These results, confirmed in a further analysis of 8740 single fibroblasts with shallow scRNAseq, suggest that the specific transcriptional profile of each gene contributes to the phenotypic variability of trisomies. We propose an improved model to understand the effects of CNA and, generally, of gene regulation on gene dosage imbalance.
Keywords
Alleles, Chromosomes, Human, Pair 13/genetics, Chromosomes, Human, Pair 18/genetics, Chromosomes, Human, Pair 8/genetics, DNA Copy Number Variations, Down Syndrome/genetics, Female, Fibroblasts, Gene Dosage, Gene Expression Profiling, Humans, Male, Models, Genetic, Mosaicism, Phenotype, RNA-Seq, Single-Cell Analysis, Transcriptome/genetics, Trisomy/genetics
Pubmed
Web of science
Open Access
Yes
Create date
13/10/2019 16:45
Last modification date
19/02/2020 6:19
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