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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.
Afiliación
  • Stamoulis G; Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva 4, Geneva, Switzerland.
  • Garieri M; Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva 4, Geneva, Switzerland.
  • Makrythanasis P; Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva 4, Geneva, Switzerland.
  • Letourneau A; Biomedical Research Institute Academy of Athens, Athens, Greece.
  • Guipponi M; Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva 4, Geneva, Switzerland.
  • Panousis N; Geneva University Hospitals, Service of Genetic Medicine, 1211 Geneva 4, Geneva, Switzerland.
  • Sloan-Béna F; Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva 4, Geneva, Switzerland.
  • Falconnet E; Geneva University Hospitals, Service of Genetic Medicine, 1211 Geneva 4, Geneva, Switzerland.
  • Ribaux P; Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva 4, Geneva, Switzerland.
  • Borel C; Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva 4, Geneva, Switzerland.
  • Santoni F; Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva 4, Geneva, Switzerland.
  • Antonarakis SE; Service of Endocrinology, Diabetes and Metabolism, University Hospital of Lausanne - CHUV, Lausanne, 1011, Switzerland. federico.santoni@chuv.ch.
Nat Commun ; 10(1): 4495, 2019 10 03.
Article en En | MEDLINE | ID: mdl-31582743
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trisomía / Dosificación de Gen / Variaciones en el Número de Copia de ADN / Transcriptoma / Modelos Genéticos Límite: Female / Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2019 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trisomía / Dosificación de Gen / Variaciones en el Número de Copia de ADN / Transcriptoma / Modelos Genéticos Límite: Female / Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2019 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Reino Unido