Activation of Embryonic Gene Transcription in Neural Precursor Cells Derived from the Induced Pluripotent Stem Cells of the Patients with Parkinson’s Disease

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Viya B. Fedoseyeva^1,a*#, Ekaterina V. Novosadova^1#, Valentina V. Nenasheva^1#, Lyudmila V. Novosadova¹, Igor A. Grivennikov¹, and Vyacheslav Z. Tarantul¹

¹National Research Center “Kurchatov Institute”, 123182 Moscow, Russia

^* To whom correspondence should be addressed.

^# These authors contributed equally to this study

Received October 31, 2022; Revised March 3, 2023; Accepted March 7, 2023

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Parkinson’s disease (PD) is one of the most common neurodegenerative diseases in the world. Despite numerous studies, the causes of this pathology remain completely unknown. This is, among other things, due to the difficulty of obtaining biological material for analysis. Neural cell cultures derived from the induced pluripotent stem cells (IPSCs) provide a great potential for studying molecular events underlying the pathogenesis of PD. This paper presents the results of bioinformatic analysis of the data obtained using RNA-seq technology in the study of neural precursors (NP) derived from IPSCs of the healthy donors and patients with PD carrying various mutations that are commonly associated with familial PD. This analysis showed that the level of transcription of multiple genes actively expressed in the nervous system at the embryonic stage of development was significantly increased in the NP cells obtained from the patients with PD, unlike in the case of healthy donors. Bioinformatic data have been, in general, confirmed using real-time PCR. The obtained data suggest that one of the causes of PD may be the shift of the gene expression pattern in neuronal cells towards embryonic gene expression pattern (termed dematuration).

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KEY WORDS: Parkinson’s disease, induced pluripotent stem cells, neural precursors, RNA-seq, differential gene expression, PCR, bioinformatic analysis

DOI: 10.1134/S0006297923040077

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