Objective: In this study, we aimed to investigate global gene expression alterations in cultured skin fibroblasts from individuals with idiopathic Parkinson’s disease (PD) compared to healthy controls (HCs).

Background: Skin fibroblasts have been proposed as a useful PD model, since they provide a system with defined mutations, able to reproduce several of the molecular changes that occur in PD. However, to the best of our knowledge, there are no previous studies that have investigated gene expression in fibroblasts of PD patients.

Method: Total RNA was extracted from fibroblast cultures of 18 individuals with PD and 13 genetically unrelated HCs.RNA concentration, purity and quality was determined using the Agilent 2100 Bioanalyzer (Agilent Technologies, Santa Clara, CA, USA). Subsequently, total RNA was used for next generation RNA sequencing using the NextSeq 2000 Sequencing System (Illumina). Global RNA sequencing and differential gene expression analysis was performed to identify differences in gene expression patterns between the two groups. Finally, we performed gene ontology enrichment analysis to define the main canonical pathways, in which, these genes were involved.

Results: In total, 518 genes were differentially expressed between PD and HCs. Filtering of low expressed genes subsequently led to totally 489 genes, with 243 genes being significantly upregulated and 275 genes downregulated in the PD group compared to healthy controls. Gene ontology enrichment analysis showed that the most significant differentially expressed genes between the two groups are mainly involved in mitosis, cell development and morphogenesis, cell adhesion and response to stimuli. Interestingly, downregulated genes are shown to be particularly involved in cell transition, migration and differentiation, while upregulated genes in cell component assembly.

Conclusion: In conclusion, our study supports the use of skin fibroblasts as a useful model for studying gene expression alterations in PD. Our results indicate distinct patterns of gene expression in fibroblasts in PD, with differentially expressed genes being involved in specific molecular pathways. Validation studies with histopathology in skin biopsies are ongoing

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MDS Abstracts - https://www.mdsabstracts.org/abstract/distinct-patterns-of-gene-expression-in-skin-biopsy-derived-fibroblasts-of-patients-with-parkinsons-disease/