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

Salvatore Vaiasicca, Gianmarco Melone, David W. James, Marcos Quintela, Alessandra Preziuso, Richard H. Finnell, Steve Conlan Orcid Logo, Lewis W. Francis, Bruna Corradetti Orcid Logo

Stem Cell Research and Therapy, Volume: 14, Issue: 1

Swansea University Author: Steve Conlan Orcid Logo

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DOI (Published version): 10.1186/s13287-023-03503-4

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 comple...

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Published in: Stem Cell Research and Therapy
ISSN: 1757-6512
Published: Springer Science and Business Media LLC 2023
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URI: https://cronfa.swan.ac.uk/Record/cronfa64628
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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.
Keywords: Chorionic villi, Mesenchymal stem cells, Down syndrome, Next-generation sequencing analysis
College: Faculty of Medicine, Health and Life Sciences
Funders: B.C. received salary support from the Sêr Cymru II program, funded by the European Commission through the Horizon 2020 Marie Skłodowska-Curie Actions (MSCA) COFUND scheme and the Welsh European Funding Office (WEFO) under the European Regional Development Fund (ERDF) and Houston Methodist Research Institute (USA).
Issue: 1

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