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Cited by 4Down syndrome and intellectual disability researchPrenatal Screening and DiagnosticsGenetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities

Transcriptomic analysis of stem cells from chorionic villi uncovers the impact of chromosomes 2, 6 and 22 in the clinical manifestations of Down syndrome

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Vaiasicca, Salvatore, Melone, Gianmarco, James, David W., Quintela, Marcos, Preziuso, Alessandra, Finnell, Richard H., Conlan, Robert Steven, Francis, Lewis W. +1 more·2023·Stem Cell Research & Therapy
DOI 10.1186/s13287-023-03503-4PMC PMC10517537
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Abstract

Background: Down syndrome (DS) clinical multisystem condition is generally considered the result of a genetic imbalance generated by the extra copy of chromosome 21. Recent discoveries, however, demonstrate that the molecular mechanisms activated in DS compared to euploid individuals are more complex than previously thought. Here, we utilize mesenchymal stem cells from chorionic villi (CV) to uncover the role of comprehensive functional genomics-based understanding of DS complexity. Methods: Next-generation sequencing coupled with bioinformatic analysis was performed on CV obtained from women carrying fetuses with DS (DS-CV) to reveal specific genome-wide transcriptional changes compared to their euploid counterparts. Functional assays were carried out to confirm the biological processes identified as enriched in DS-CV compared to CV (i.e., cell cycle, proliferation features, immunosuppression and ROS production). Results: Genes located on chromosomes other than the canonical 21 (Ch. 2, 6 and 22) are responsible for the impairment of life-essential pathways, including cell cycle regulation, innate immune response and reaction to external stimuli were found to be differentially expressed in DS-CV. Experimental validation confirmed the key role of the biological pathways regulated by those genes in the etiology of such a multisystem condition. Conclusions: NGS dataset generated in this study highlights the compromised functionality in the proliferative rate and in the innate response of DS-associated clinical conditions and identifies DS-CV as suitable tools for the development of specifically tailored, personalized intervention modalities.

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Sorted by citations

Authors
Vaiasicca, S., Melone, G., James, D. W., Quintela, M., Preziuso, A., Finnell, R. H., Conlan, R. S., Francis, L. W., & Corradetti, B.
Affiliations
  • Marche Polytechnic University (IT)
  • Swansea University (GB)
  • Baylor College of Medicine (US)
  • Houston Methodist (US)
Corresponding author
Corradetti, Bruna
ORCID
Venue
Stem Cell Research & Therapy
Publisher
Springer Science and Business Media LLC
Published
2023-09-23
Volume
14
Issue
1
Pages
265-265
ISSN
1757-6512 (ISSN-L)
DOI
10.1186/s13287-023-03503-4
PMC
PMC10517537
OpenAlex
W4386979665
Cited by
4
References
6
Citations by year
2025: 1 · 2024: 3
FWCI
1.02
Type
journal article
Language
en
Open access
Licence
Locations
  • Stem Cell Research & Therapy (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Digital Commons-TMC (Texas Medical Center) (submittedVersion)
  • Cronfa (Swansea University) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
Funders
  • European Commission (HORIZON2020)
  • Houston Methodist Research Institute
  • European Regional Development Fund
  • H2020 Marie Skłodowska-Curie Actions (HORIZON2020)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Screening and Diagnostics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
Keywords
Down syndrome, chorionic villi, mesenchymal stem cells, transcriptome, chromosome 2, chromosome 6, chromosome 22, cell cycle regulation, cell proliferation, innate immune response, immunosuppression, reactive oxygen species, gene expression profiling, personalized medicine
MeSH terms
Chorionic Villi, Chromosomes, Down Syndrome, Female, Humans, Stem Cells, Transcriptome

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