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Cited by 141Down syndrome and intellectual disability researchAdvanced Proteomics Techniques and ApplicationsGenetics and Neurodevelopmental Disorders

Systematic proteome and proteostasis profiling in human trisomy 21 fibroblast cells

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Liu, Yansheng, Borel, Christelle, Li, Li, Müller, Torsten, Williams, Evan G., Germain, Pierre-Luc, Buljan, Marija, Sajic, Tatjana +7 more·2017·Nature Communications
DOI 10.1038/s41467-017-01422-6PMC PMC5663699
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Abstract

Down syndrome (DS) is mostly caused by a trisomy of the entire Chromosome 21 (Trisomy 21, T21). Here, we use SWATH mass spectrometry to quantify protein abundance and protein turnover in fibroblasts from a monozygotic twin pair discordant for T21, and to profile protein expression in 11 unrelated DS individuals and matched controls. The integration of the steady-state and turnover proteomic data indicates that protein-specific degradation of members of stoichiometric complexes is a major determinant of T21 gene dosage outcome, both within and between individuals. This effect is not apparent from genomic and transcriptomic data. The data also reveal that T21 results in extensive proteome remodeling, affecting proteins encoded by all chromosomes. Finally, we find broad, organelle-specific post-transcriptional effects such as significant downregulation of the mitochondrial proteome contributing to T21 hallmarks. Overall, we provide a valuable proteomic resource to understand the origin of DS phenotypic manifestations.

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  • In trisomic fibroblasts, some trisomic transcripts were upregulated but the corresponding proteins were not (or vice versa), and those differences are hypothesized to reflect post transcriptional regulation, maintenance of stoichiometry of protein complexes, or buffering.

    “Others have shown in trisomic fibroblasts that some trisomic transcripts were upregulated but the corresponding proteins were not (or vice versa), and hypothesize those differences reflect post transcriptional regulation, maintenance of stoichiometry of protein complexes, or buffering (Liu et al., 2017).”

    From Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model (2024) · cites this paper as Liu et al., 2017

  • Post transcriptional regulation and turnover, especially of trisomic proteins, was shown to account for differences between transcriptome and proteome products.

    “Post transcriptional regulation and turnover, especially of trisomic proteins, was shown to account for differences between transcriptome and proteome products.”

    From Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model (2024) · cites this paper as Liu et al., 2017

  • Changes in mRNA and protein levels correlated only weakly both when assessing individuals with DS as compared to those without DS and when comparing a discordant trisomic twin pair.

    “changes only correlated weakly both when assessing individuals with DS as compared to those without DS and when comparing a discordant trisomic twin pair”

    From Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model (2024) · cites this paper as Liu et al., 2017

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Cited by

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Authors
Liu, Y., Borel, C., Li, L., Müller, T., Williams, E. G., Germain, P.-L., Buljan, M., Sajic, T., Boersema, P. J., Shao, W., Faini, M., Testa, G., Beyer, A., Antonarakis, S. E., & Aebersold, R.
Affiliations
  • ETH Zurich (CH)
  • University of Geneva (CH)
  • University of Cologne (DE)
  • European Institute of Oncology (IT)
  • University of Milan (IT)
  • University of Zurich (CH)
Corresponding author
  • Beyer, Andreas
  • Antonarakis, Stylianos E.
  • Aebersold, Ruedi
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2017-10-31
Volume
8
Issue
1
Pages
1212-1212
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-017-01422-6
PMC
PMC5663699
OpenAlex
W2766220585
Cited by
141
References
10
Citations by year
2026: 10 · 2025: 13 · 2024: 19 · 2023: 16 · 2022: 20 · 2021: 14 · 2020: 18 · 2019: 19 · 2018: 11
FWCI
12.33
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
  • Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
  • Open Repository and Bibliography (University of Luxembourg) (submittedVersion, cc-by-nc-sa)
  • Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
  • ETH Zürich Research Collection (cc-by)
Funders
  • National Science Foundation
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (163180, 166435)
  • Bundesministerium für Bildung und Forschung
  • Ministero della Salute
  • Regione Lombardia
  • SystemsX.ch
  • H2020 European Research Council (670821)
  • FP7 Ideas: European Research Council (233226, 616441, 249968)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
Down syndrome, proteomic profiling, proteostasis, protein turnover, protein degradation, gene dosage, monozygotic twin discordance, fibroblasts, post-transcriptional regulation, proteome remodeling
MeSH terms
Proteostasis, Dosage Compensation, Genetic, Fibroblasts, Gene Expression Regulation, Humans, Trisomy, Organelles, Signal Transduction, Proteome, Mitochondrial Proteins, Databases, Protein, Proteolysis

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