TY - JOUR

T1 - IPSC-Derived Astrocytes Contribute to In Vitro Modeling of Parkinson's Disease Caused by the GBA1 N370S Mutation

AU - Yarkova, Elena S

AU - Grigor'eva, Elena V

AU - Medvedev, Sergey P

AU - Pavlova, Sophia V

AU - Zakian, Suren M

AU - Malakhova, Anastasia A

N1 - This research was funded by the Russian Science Foundation, grant number 23-15-00224. Публикация для корректировки.

PY - 2024/1

Y1 - 2024/1

N2 - Parkinson's disease (PD) is a neurodegenerative disorder that ranks second in prevalence after Alzheimer's disease. The number of PD diagnoses increases annually. Nevertheless, modern PD treatments merely mitigate symptoms rather than preventing neurodegeneration progression. The creation of an appropriate model to thoroughly study the mechanisms of PD pathogenesis remains a current challenge in biomedicine. Recently, there has been an increase in data regarding the involvement of not only dopaminergic neurons of the substantia nigra but also astrocytes in the pathogenesis of PD. Cell models based on induced pluripotent stem cells (iPSCs) and their differentiated derivatives are a useful tool for studying the contribution and interaction of these two cell types in PD. Here, we generated two iPSC lines, ICGi034-B and ICGi034-C, by reprogramming peripheral blood mononuclear cells of a patient with a heterozygous mutation c.1226A>G (p.N370S) in the GBA1 gene by non-integrating episomal vectors encoding OCT4, KLF4, L-MYC, SOX2, LIN28, and mp53DD. The iPSC lines demonstrate the expression of pluripotency markers and are capable of differentiating into three germ layers. We differentiated the ICGi034-B and ICGi034-C iPSC lines into astrocytes. This resulting cell model can be used to study the involvement of astrocytes in the pathogenesis of GBA-associated PD.

AB - Parkinson's disease (PD) is a neurodegenerative disorder that ranks second in prevalence after Alzheimer's disease. The number of PD diagnoses increases annually. Nevertheless, modern PD treatments merely mitigate symptoms rather than preventing neurodegeneration progression. The creation of an appropriate model to thoroughly study the mechanisms of PD pathogenesis remains a current challenge in biomedicine. Recently, there has been an increase in data regarding the involvement of not only dopaminergic neurons of the substantia nigra but also astrocytes in the pathogenesis of PD. Cell models based on induced pluripotent stem cells (iPSCs) and their differentiated derivatives are a useful tool for studying the contribution and interaction of these two cell types in PD. Here, we generated two iPSC lines, ICGi034-B and ICGi034-C, by reprogramming peripheral blood mononuclear cells of a patient with a heterozygous mutation c.1226A>G (p.N370S) in the GBA1 gene by non-integrating episomal vectors encoding OCT4, KLF4, L-MYC, SOX2, LIN28, and mp53DD. The iPSC lines demonstrate the expression of pluripotency markers and are capable of differentiating into three germ layers. We differentiated the ICGi034-B and ICGi034-C iPSC lines into astrocytes. This resulting cell model can be used to study the involvement of astrocytes in the pathogenesis of GBA-associated PD.

KW - Humans

KW - Astrocytes

KW - Induced Pluripotent Stem Cells

KW - Leukocytes, Mononuclear

KW - Mutation

KW - Parkinson Disease/genetics

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85182097176&origin=inward&txGid=d667b9e6e77cbb77a2c1e99dd3d7be3a

UR - https://www.mendeley.com/catalogue/cfde0b38-068f-3835-bbe1-43d955e5f359/

U2 - 10.3390/ijms25010327

DO - 10.3390/ijms25010327

M3 - Article

C2 - 38203497

VL - 25

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 1

M1 - 327

ER -