Transcriptomic differences in MSA clinical variants

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  • dc.contributor.author Pérez Soriano, Alexandra
  • dc.contributor.author Arnal, Magdalena
  • dc.contributor.author Botta Orfila, Teresa
  • dc.contributor.author Giraldo, Darly
  • dc.contributor.author Fernández, Manel
  • dc.contributor.author Compta, Yaroslau
  • dc.contributor.author Fernández-Santiago, Ruben
  • dc.contributor.author Ezquerra, Mario
  • dc.contributor.author Tartaglia, Gian Gaetano
  • dc.contributor.author Martí, M. Josep
  • dc.contributor.author Catalan multiple system atrophy-registry (CMSAR)
  • dc.date.accessioned 2020-10-16T06:34:10Z
  • dc.date.available 2020-10-16T06:34:10Z
  • dc.date.issued 2020
  • dc.description.abstract Background: Multiple system atrophy (MSA) is a rare oligodendroglial synucleinopathy of unknown etiopathogenesis including two major clinical variants with predominant parkinsonism (MSA-P) or cerebellar dysfunction (MSA-C). Objective: To identify novel disease mechanisms we performed a blood transcriptomic study investigating differential gene expression changes and biological process alterations in MSA and its clinical subtypes. Methods: We compared the transcriptome from rigorously gender and age-balanced groups of 10 probable MSA-P, 10 probable MSA-C cases, 10 controls from the Catalan MSA Registry (CMSAR), and 10 Parkinson Disease (PD) patients. Results: Gene set enrichment analyses showed prominent positive enrichment in processes related to immunity and inflammation in all groups, and a negative enrichment in cell differentiation and development of the nervous system in both MSA-P and PD, in contrast to protein translation and processing in MSA-C. Gene set enrichment analysis using expression patterns in different brain regions as a reference also showed distinct results between the different synucleinopathies. Conclusions: In line with the two major phenotypes described in the clinic, our data suggest that gene expression and biological processes might be differentially affected in MSA-P and MSA-C. Future studies using larger sample sizes are warranted to confirm these results.
  • dc.description.sponsorship We would like to thank all the patients for their always willing and generous collaboration. This project has been possible thanks to the funding from the Fundació Marató TV3 and CERCA Programme from Generalitat de Catalunya. We also thank the European Research Council RIBOMYLOME_309545 and Spanish Ministry of Economy and Competitiveness (BFU2017-86970-P). A.P.-S. was funded by a PHD4MD grant, which is a collaborative research training program for medical doctors. R.F.-S. was supported by a Jóvenes Investigadores (JIN) grant of the Spanish Ministry of Economy and Competitiveness (MINECO) and the Agencia Estatal de Investigación (AEI) (AEI/FEDER/UE) (grant # SAF2015-73508-JIN), and a Miguel Servet grant from the Instituto de Salud Carlos III (grant # CP19/00048). M.F. was funded by María de Maeztu programme (grant # MDM-2017-0729). Thanks to Lara Nonell, head of the Human Computational Biology group in IMIM, for offering the computational resources in the institution and the help with data management.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Pérez-Soriano A, Arnal Segura M, Botta-Orfila T, Giraldo D, Fernández M, Compta Y, Fernández-Santiago R, Ezquerra M, Tartaglia GG, Martí MJ; Catalan MSA Registry (CMSAR). Transcriptomic differences in MSA clinical variants. Sci Rep. 2020; 10(1):10310. DOI: 10.1038/s41598-020-66221-4
  • dc.identifier.doi http://dx.doi.org/10.1038/s41598-020-66221-4
  • dc.identifier.issn 2045-2322
  • dc.identifier.uri http://hdl.handle.net/10230/45499
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Sci Rep. 2020; 10(1):10310
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/309545
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-86970-P
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-73508-JIN
  • dc.rights © The Author(s) 2020. 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/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Computational biology and bioinformatics
  • dc.subject.keyword Movement disorders
  • dc.subject.keyword Neurological disorders
  • dc.subject.keyword Neurology
  • dc.subject.keyword Neuroscience
  • dc.title Transcriptomic differences in MSA clinical variants
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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