Creation of Induced Pluripotent Stem Cells ICGi044-B and ICGi044-C Using Reprogramming of Peripheral Blood Mononuclear Cells of a Patient with Parkinson’s Disease Associated with c.1492T>G Mutation in the GLUD2 Gene

• Published in: Russian journal of developmental biology Vol. 54; no. 1; pp. 104 - 111
• Main Authors: Sorogina, D. A., Grigor’eva, E. V., Malakhova, A. A., Pavlova, S. V., Medvedev, S. P., Vyatkin, Y. V., Khabarova, E. A., Rzaev, J. A., Zakian, S. M.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 2023; Springer Nature B.V
• Subjects: Age; Animal Anatomy; Biomedical and Life Sciences; Cell culture; Collection of Pluripotent Stem Cell Lines; Developmental Biology; Environmental factors; Genetic diversity; Histology; Karyotypes; KLF4 protein; Leukocytes (mononuclear); Life Sciences; Morphology; Movement disorders; Mutation; Myc protein; Neurodegenerative diseases; Oct-4 protein; p53 Protein; Parkinson's disease; Peripheral blood mononuclear cells; Pluripotency; Single-nucleotide polymorphism; Stem cells; reprogramming; induced pluripotent stem cells; polymorphisms; Parkinson’s disease
• ISSN: 1062-3604; 1608-3326
• DOI: 10.1134/S1062360423010125

Parkinson’s disease is a multifactorial disease; both genetic predisposition (5% of all cases), environmental factors, and age-related changes in the brain and other body systems contribute to its etiology. For the diagnosis and study of the pathology of the disease development, it is important to search for new polymorphisms associated with hereditary forms of the disease. The clinical exome of a 55-year-old patient with Parkinson’s disease was analyzed and a single nucleotide polymorphism in the GLUD2 gene ( c.1492T>G ) was identified. This genetic variant is pathogenic according to the ClinVar database, but the mechanism of pathogenesis is still poorly understood. In addition, there are currently no relevant models based on human cells, which is of great interest. We generated induced pluripotent stem cells (iPSCs) from patient peripheral blood mononuclear cells using nonintegrating episomal vectors expressing OCT4, KLF4, L-MYC, SOX2, LIN28, and p53 shRNA. The obtained iPSC lines (ICGi044-B and ICGi044-C) demonstrate typical ESC-like morphology, normal karyotype (46,XY), express pluripotency markers (OCT4, SOX2, NANOG, SSEA4, TRA‑1-60), and are able to give derivatives of three germ layers. The iPSC lines ICGi044-B and ICGi044-C, as well as their neural derivatives, represent a unique in vitro cell model for studying the pathogenetic mechanisms of the development of Parkinson’s disease associated with the c.1492T>G mutation in the GLUD2 gene.