Generation of an Induced Pluripotent Stem Cell Line, ICGi043-A, by Reprogramming Peripheral Blood Mononuclear Cells from Parkinson’s Disease Patient with p.G2019S Mutation in  LRRK2  Gene

E. V. Grigor’eva; Григорьева Е. В.; S. P. Medvedev; Медведев С. П.; S. N. Pchelina; Пчелина С. Н.; M. A. Nikolaev; Николаев М. А.; I. V. Miliukhina; Милюхина И. В.; J. M. Minina; Минина Ю. М.; D. A. Sorogina; Сорогина Д. А.; E. S. Yarkova; Яркова Е. С.; A. A. Malakhova; Малахова А. А.; S. V. Pavlova; Павлова С. В.; S. M. Zakian; Закиян С. М.

doi:10.31857/S0475145023010056

Generation of an Induced Pluripotent Stem Cell Line, ICGi043-A, by Reprogramming Peripheral Blood Mononuclear Cells from Parkinson’s Disease Patient with p.G2019S Mutation in LRRK2 Gene

Authors: Grigor’eva E.V.¹, Medvedev S.P.¹, Pchelina S.N.², Nikolaev M.A.², Miliukhina I.V.³, Minina J.M.¹, Sorogina D.A.¹, Yarkova E.S.¹, Malakhova A.A.¹, Pavlova S.V.¹, Zakian S.M.¹
Affiliations:
1. Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
2. Pavlov First Saint Petersburg State Medical University
3. Behtereva Institute of the Human Brain of the Russian Academy of Sciences
Issue: Vol 54, No 1 (2023)
Pages: 79-86
Section: Collection of pluripotent stem cell lines
URL: https://journals.rcsi.science/0475-1450/article/view/137045
DOI: https://doi.org/10.31857/S0475145023010056
EDN: https://elibrary.ru/FQQEBY
ID: 137045

Cite item

Full Text

Open Access
Restricted Access

Access granted
Restricted Access

Subscription Access

Abstract
About the authors
References
Supplementary files
Statistics

Abstract

The pathological variant p.G2019S in the LRRK2 gene leads to the occurrence of a hereditary form of Parkinson’s disease (PD) and affects 7% of patients with a familial form of the disease. However, the mechanisms that trigger pathological events during the development of the disease are not yet fully understood. We obtained iPSCs (ICGi043-A line) from peripheral blood mononuclear cells of a patient with a hereditary form of PD associated with the genetic variant c.6055G>A (p.G2019S, rs34637584) in the LRRK2 gene using transfection with episomal vectors. iPSCs rapidly proliferate in dense monolayer cell colonies, are positive for endogenous alkaline phosphatase, have a normal karyotype (46,XX), express pluripotency markers (OCT4, SOX2, NANOG, TRA-1-60, SSEA-4) and are able to differentiate into three germ layers (ecto-, endo- and mesoderm), which confirms their pluripotent status. Future directed differentiation of the obtained iPSCs into dopaminergic neurons will allow the creation of an in vitro cell model of PD associated with the pathological variant c.6055G>A in the LRRK2 gene, and contribute to understanding the pathogenesis of PD.

Keywords

Parkinson’s disease, induced pluripotent stem cells, polymorphisms, reprogramming

References

Пчелина С.Н., Иванова О.Н., Емельянов А.К., Якимовский А.Ф. Клиническое течение LRRK2-ассоциированной болезни Паркинсона // Журн. неврологии и психиатрии. 2011. Т. 12. С. 56–62.
Choppa P.C., Vojdani A., Tagle C. et al. Multiplex PCR for the detection of Mycoplasma fermentans, M. hominis and M. penetrans in cell cultures and blood samples of patients with chronic fatigue syndrome // Mol. Cell Probes. 1998. V. 12. № 5. P. 301–308.
Grigor’eva E.V., Malankhanova T.B., Surumbayeva A. et al. Generation of GABAergic striatal neurons by a novel iPSC differentiation protocol enabling scalability and cryopreservation of progenitor cells // Cytotechnology. 2020. V. 72. № 5. P. 649–663.
Okita K., Yamakawa T., Matsumura Y. et al. An efficient nonviral method to generate integration-free human-induced pluripotent stem cells from cord blood and peripheral blood cells // Stem Cells. 2013. V. 31. № 3. P. 458–466.
Pchelina S.N., Yakimovskii A.F., Ivanova O.N., Emelianov A.K., Zakharchuk A.H., Schwarzman A.L. G2019S LRRK2 mutation in familial and sporadic Parkinson’s disease in Russia // Mov. Disord. 2006. V. 21. № 12. P. 2234–2236.