Generation and characterisation of seven induced pluripotent stem cell lines from two patients with Parkinson’s disease carrying the pathological variant c.1087G>T of the <i>LGR4</i> gene
Parkinson’s disease is a neurodegenerative disorder affecting dopaminergic neurons of the substantia nigra pars compacta. The known pathological genetic variants may explain the cause of only 5 % of cases of the disease. In our study, we found two patients with a clinical diagnosis of Parkinson’s di...
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Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
2025-03-01
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| Series: | Вавиловский журнал генетики и селекции |
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| Online Access: | https://vavilov.elpub.ru/jour/article/view/4469 |
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| author | V. S. Podvysotskaya E. V. Grigor’eva A. A. Malakhova J. M. Minina Y. V. Vyatkin E. A. Khabarova J. A. Rzaev S. P. Medvedev L. V. Kovalenko S. M. Zakian |
| author_facet | V. S. Podvysotskaya E. V. Grigor’eva A. A. Malakhova J. M. Minina Y. V. Vyatkin E. A. Khabarova J. A. Rzaev S. P. Medvedev L. V. Kovalenko S. M. Zakian |
| author_sort | V. S. Podvysotskaya |
| collection | DOAJ |
| description | Parkinson’s disease is a neurodegenerative disorder affecting dopaminergic neurons of the substantia nigra pars compacta. The known pathological genetic variants may explain the cause of only 5 % of cases of the disease. In our study, we found two patients with a clinical diagnosis of Parkinson’s disease with the genetic va riant c.1087G>T (p.Gly363Cys) of the LGR4 gene. The LGR4 gene encodes the membrane receptor LGR4 (leucine rich repeat containing G protein-coupled receptor 4) associated with the G protein. We hypothesize that the LGR4 gene may be either a direct cause or a risk factor for this disease, since it is one of the main participants of the WNT/β-catenin signalling pathway. This signalling pathway is necessary for the proliferation of neurons during their differentiation, which may lead to Parkinson’s disease. To study the relationship between this genetic variant and Parkinson’s disease, an ideal tool is a cellular model based on induced pluripotent stem cells (iPSCs) and their differentiated derivatives, dopaminergic neurons. We reprogrammed the peripheral blood mononuclear cells of the two patients with the c.1087G>T variant of the LGR4 gene with non-integrating episomal vectors expressing OCT4, SOX2, KLF4, LIN28, L-MYC and mp53DD proteins. The obtained seven lines of induced pluripotent stem cells were characterised in detail. The iPSCs lines obtained meet all the requirements of pluripotent cells, namely, they stably proliferate, form colonies with a morphology characteristic of human pluripotent cells, have a normal diploid karyotype, express endogenous alkaline phosphatase and pluripotency markers (OCT4, NANOG, SSEA-4 and SOX2) and are capable to differentiate into derivatives of the three germ layers. The iPSC lines obtained in this work can be used as a tool to generate a relevant model to study the effect of the pathological variant c.1087G>T of the LGR4 gene on dopaminergic neuron differentiation. |
| format | Article |
| id | doaj-art-c1bba07b1197495c9fcde7bb91a8c793 |
| institution | Kabale University |
| issn | 2500-3259 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders |
| record_format | Article |
| series | Вавиловский журнал генетики и селекции |
| spelling | doaj-art-c1bba07b1197495c9fcde7bb91a8c7932025-08-20T03:44:11ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592025-03-01291152510.18699/vjgb-25-031538Generation and characterisation of seven induced pluripotent stem cell lines from two patients with Parkinson’s disease carrying the pathological variant c.1087G>T of the <i>LGR4</i> geneV. S. Podvysotskaya0E. V. Grigor’eva1A. A. Malakhova2J. M. Minina3Y. V. Vyatkin4E. A. Khabarova5J. A. Rzaev6S. P. Medvedev7L. V. Kovalenko8S. M. Zakian9Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State UniversityInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesNOVEL Ltd.Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Federal Neurosurgical Center of the Ministry of Health of the Russian FederationFederal Neurosurgical Center of the Ministry of Health of the Russian FederationInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of SciencesSurgut State UniversityInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of SciencesParkinson’s disease is a neurodegenerative disorder affecting dopaminergic neurons of the substantia nigra pars compacta. The known pathological genetic variants may explain the cause of only 5 % of cases of the disease. In our study, we found two patients with a clinical diagnosis of Parkinson’s disease with the genetic va riant c.1087G>T (p.Gly363Cys) of the LGR4 gene. The LGR4 gene encodes the membrane receptor LGR4 (leucine rich repeat containing G protein-coupled receptor 4) associated with the G protein. We hypothesize that the LGR4 gene may be either a direct cause or a risk factor for this disease, since it is one of the main participants of the WNT/β-catenin signalling pathway. This signalling pathway is necessary for the proliferation of neurons during their differentiation, which may lead to Parkinson’s disease. To study the relationship between this genetic variant and Parkinson’s disease, an ideal tool is a cellular model based on induced pluripotent stem cells (iPSCs) and their differentiated derivatives, dopaminergic neurons. We reprogrammed the peripheral blood mononuclear cells of the two patients with the c.1087G>T variant of the LGR4 gene with non-integrating episomal vectors expressing OCT4, SOX2, KLF4, LIN28, L-MYC and mp53DD proteins. The obtained seven lines of induced pluripotent stem cells were characterised in detail. The iPSCs lines obtained meet all the requirements of pluripotent cells, namely, they stably proliferate, form colonies with a morphology characteristic of human pluripotent cells, have a normal diploid karyotype, express endogenous alkaline phosphatase and pluripotency markers (OCT4, NANOG, SSEA-4 and SOX2) and are capable to differentiate into derivatives of the three germ layers. The iPSC lines obtained in this work can be used as a tool to generate a relevant model to study the effect of the pathological variant c.1087G>T of the LGR4 gene on dopaminergic neuron differentiation.https://vavilov.elpub.ru/jour/article/view/4469parkinson’s diseasereprogramminginduced pluripotent stem cells<i>lgr4</i> gene |
| spellingShingle | V. S. Podvysotskaya E. V. Grigor’eva A. A. Malakhova J. M. Minina Y. V. Vyatkin E. A. Khabarova J. A. Rzaev S. P. Medvedev L. V. Kovalenko S. M. Zakian Generation and characterisation of seven induced pluripotent stem cell lines from two patients with Parkinson’s disease carrying the pathological variant c.1087G>T of the <i>LGR4</i> gene Вавиловский журнал генетики и селекции parkinson’s disease reprogramming induced pluripotent stem cells <i>lgr4</i> gene |
| title | Generation and characterisation of seven induced pluripotent stem cell lines from two patients with Parkinson’s disease carrying the pathological variant c.1087G>T of the <i>LGR4</i> gene |
| title_full | Generation and characterisation of seven induced pluripotent stem cell lines from two patients with Parkinson’s disease carrying the pathological variant c.1087G>T of the <i>LGR4</i> gene |
| title_fullStr | Generation and characterisation of seven induced pluripotent stem cell lines from two patients with Parkinson’s disease carrying the pathological variant c.1087G>T of the <i>LGR4</i> gene |
| title_full_unstemmed | Generation and characterisation of seven induced pluripotent stem cell lines from two patients with Parkinson’s disease carrying the pathological variant c.1087G>T of the <i>LGR4</i> gene |
| title_short | Generation and characterisation of seven induced pluripotent stem cell lines from two patients with Parkinson’s disease carrying the pathological variant c.1087G>T of the <i>LGR4</i> gene |
| title_sort | generation and characterisation of seven induced pluripotent stem cell lines from two patients with parkinson s disease carrying the pathological variant c 1087g t of the i lgr4 i gene |
| topic | parkinson’s disease reprogramming induced pluripotent stem cells <i>lgr4</i> gene |
| url | https://vavilov.elpub.ru/jour/article/view/4469 |
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