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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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Abstract

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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Abbreviations

DA neurons:

dopaminergic neurons

DEGs:

differentially expressed genes

FDR:

false discovery rate

HD:

healthy donor

IPSC:

induced pluripotent stem cells

NP:

neural precursors

PD:

Parkinson’s disease

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Acknowledgments

The authors express their gratitude to academician S. N. Illarioshkin (Research Center of Neurology) for providing biopsy sample from the patients with PD, to professor M. A. Lagarkova (Federal Research and Clinical Center of Physical Chemical Medicine of the Federal Medical and Biological Agency of the Russian Federation, Moscow, Russia) for providing IPSC cell lines. Experiments were conducted with the equipment of the Center of Collective Use of scientific equipment (Center “Cellular and Genetic Technologies” of Institute of Molecular Genetics of National Research Centre “Kurchatov Institute”).

Funding

The study was financially supported by the Ministry of Science and Higher Education of the Russian Federation (agreement no. 075-15-2021-1357) (generation of cell lines) and by the Russian Science Foundation (project no. 21-15-00103) (bioinformatic analysis).

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    Authors and Affiliations

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

      Viya B. Fedoseyeva, Ekaterina V. Novosadova, Valentina V. Nenasheva, Lyudmila V. Novosadova, Igor A. Grivennikov & Vyacheslav Z. Tarantul

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    1. Viya B. Fedoseyeva
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    2. Ekaterina V. Novosadova
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    3. Valentina V. Nenasheva
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    4. Lyudmila V. Novosadova
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    5. Igor A. Grivennikov
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    6. Vyacheslav Z. Tarantul
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    Contributions

    All authors provided contribution to the development of concept and design of the study. E. V. Novosadova and V. V. Nenasheva prepared material for examination; E. V. Novosadova, L. V. Novosadova, V. V. Nenasheva, I. A. Grivennikov, and V. B. Fedoseyeva collected and analyzed the data. First draft of the paper was prepared by V. B. Fedoseyeva and V. Z. Tarantul. All authors approved final version of the manuscript.

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    Correspondence to Viya B. Fedoseyeva.

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    The authors declare no conflict of interest in financial or any other sphere. This article does not contain any studies with human participants or animals performed by any of the authors. Description of cell lines produced from human cells obtained with their consent is presented in our previous papers, where these cell lines were first introduced.

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    Fedoseyeva, V.B., Novosadova, E.V., Nenasheva, V.V. et al. Activation of Embryonic Gene Transcription in Neural Precursor Cells Derived from the Induced Pluripotent Stem Cells of the Patients with Parkinson’s Disease. Biochemistry Moscow 88, 515–525 (2023). https://doi.org/10.1134/S0006297923040077

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    • DOI: https://doi.org/10.1134/S0006297923040077

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