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Single cell transcriptome in aneuploidies reveals mechanisms of gene dosage imbalance
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 mo...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776538/ https://www.ncbi.nlm.nih.gov/pubmed/31582743 http://dx.doi.org/10.1038/s41467-019-12273-8 |
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author | Stamoulis, Georgios Garieri, Marco Makrythanasis, Periklis Letourneau, Audrey Guipponi, Michel Panousis, Nikolaos Sloan-Béna, Frédérique Falconnet, Emilie Ribaux, Pascale Borel, Christelle Santoni, Federico Antonarakis, Stylianos E. |
author_facet | Stamoulis, Georgios Garieri, Marco Makrythanasis, Periklis Letourneau, Audrey Guipponi, Michel Panousis, Nikolaos Sloan-Béna, Frédérique Falconnet, Emilie Ribaux, Pascale Borel, Christelle Santoni, Federico Antonarakis, Stylianos E. |
author_sort | Stamoulis, Georgios |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6776538 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-67765382019-10-07 Single cell transcriptome in aneuploidies reveals mechanisms of gene dosage imbalance Stamoulis, Georgios Garieri, Marco Makrythanasis, Periklis Letourneau, Audrey Guipponi, Michel Panousis, Nikolaos Sloan-Béna, Frédérique Falconnet, Emilie Ribaux, Pascale Borel, Christelle Santoni, Federico Antonarakis, Stylianos E. Nat Commun Article 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. Nature Publishing Group UK 2019-10-03 /pmc/articles/PMC6776538/ /pubmed/31582743 http://dx.doi.org/10.1038/s41467-019-12273-8 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Stamoulis, Georgios Garieri, Marco Makrythanasis, Periklis Letourneau, Audrey Guipponi, Michel Panousis, Nikolaos Sloan-Béna, Frédérique Falconnet, Emilie Ribaux, Pascale Borel, Christelle Santoni, Federico Antonarakis, Stylianos E. Single cell transcriptome in aneuploidies reveals mechanisms of gene dosage imbalance |
title | Single cell transcriptome in aneuploidies reveals mechanisms of gene dosage imbalance |
title_full | Single cell transcriptome in aneuploidies reveals mechanisms of gene dosage imbalance |
title_fullStr | Single cell transcriptome in aneuploidies reveals mechanisms of gene dosage imbalance |
title_full_unstemmed | Single cell transcriptome in aneuploidies reveals mechanisms of gene dosage imbalance |
title_short | Single cell transcriptome in aneuploidies reveals mechanisms of gene dosage imbalance |
title_sort | single cell transcriptome in aneuploidies reveals mechanisms of gene dosage imbalance |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776538/ https://www.ncbi.nlm.nih.gov/pubmed/31582743 http://dx.doi.org/10.1038/s41467-019-12273-8 |
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