Transcriptome Analysis of Induced Pluripotent Stem Cells and Neuronal Progenitor Cells, Derived from Discordant Monozygotic Twins with Parkinson’s Disease
Ivan N. Vlasov,
Anelya Kh. Alieva,
Ekaterina V. Novosadova,
Elena L. Arsenyeva,
Anna V. Rosinskaya,
Suzanna A. Partevian,
Igor A. Grivennikov,
Maria I. Shadrina
Affiliations
Ivan N. Vlasov
Institute of Molecular Genetics of National Research Centre, Kurchatov Institute, 2 Kurchatova Sq., 123182 Moscow, Russia
Anelya Kh. Alieva
Institute of Molecular Genetics of National Research Centre, Kurchatov Institute, 2 Kurchatova Sq., 123182 Moscow, Russia
Ekaterina V. Novosadova
Institute of Molecular Genetics of National Research Centre, Kurchatov Institute, 2 Kurchatova Sq., 123182 Moscow, Russia
Elena L. Arsenyeva
Institute of Molecular Genetics of National Research Centre, Kurchatov Institute, 2 Kurchatova Sq., 123182 Moscow, Russia
Anna V. Rosinskaya
State Public Health Institution Primorsk Regional Clinical Hospital No. 1, 57 Aleutskaya St., 690091 Vladivostok, Russia
Suzanna A. Partevian
Institute of Molecular Genetics of National Research Centre, Kurchatov Institute, 2 Kurchatova Sq., 123182 Moscow, Russia
Igor A. Grivennikov
Institute of Molecular Genetics of National Research Centre, Kurchatov Institute, 2 Kurchatova Sq., 123182 Moscow, Russia
Maria I. Shadrina
Institute of Molecular Genetics of National Research Centre, Kurchatov Institute, 2 Kurchatova Sq., 123182 Moscow, Russia
Parkinson’s Disease (PD) is a widespread severe neurodegenerative disease that is characterized by pronounced deficiency of the dopaminergic system and disruption of the function of other neuromodulator systems. Although heritable genetic factors contribute significantly to PD pathogenesis, only a small percentage of sporadic cases of PD can be explained using known genetic risk factors. Due to that, it could be inferred that changes in gene expression could be important for explaining a significant percentage of PD cases. One of the ways to investigate such changes, while minimizing the effect of genetic factors on experiment, are the study of PD discordant monozygotic twins. In the course of the analysis of transcriptome data obtained from IPSC and NPCs, 20 and 1906 differentially expressed genes were identified respectively. We have observed an overexpression of TNF in NPC cultures, derived from twin with PD. Through investigation of gene interactions and gene involvement in biological processes, we have arrived to a hypothesis that TNF could play a crucial role in PD-related changes occurring in NPC derived from twins with PD, and identified INHBA, WNT7A and DKK1 as possible downstream effectors of TNF.