Isogenic induced pluripotent stem cell line ICGi036-A-1 from a patient with familial hypercholesterolaemia, derived by correcting a pathogenic variant of the gene LDLR c.530C>T
Familial hypercholesterolaemia is a common monogenic disorder characterized by high plasma cholesterol levels leading to chronic cardiovascular disease with high risk and often early manifestation due to atherosclerotic lesions of the blood vessels. The atherosclerotic lesions in familial hyperchole...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
2025-04-01
|
| Series: | Вавиловский журнал генетики и селекции |
| Subjects: | |
| Online Access: | https://vavilov.elpub.ru/jour/article/view/4537 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1839572366930214912 |
|---|---|
| author | A. S. Zueva A. I. Shevchenko S. P. Medvedev E. A. Elisaphenko A. A. Sleptcov M. S. Nazarenko N. A. Tmoyan S. M. Zakian I. S. Zakharova |
| author_facet | A. S. Zueva A. I. Shevchenko S. P. Medvedev E. A. Elisaphenko A. A. Sleptcov M. S. Nazarenko N. A. Tmoyan S. M. Zakian I. S. Zakharova |
| author_sort | A. S. Zueva |
| collection | DOAJ |
| description | Familial hypercholesterolaemia is a common monogenic disorder characterized by high plasma cholesterol levels leading to chronic cardiovascular disease with high risk and often early manifestation due to atherosclerotic lesions of the blood vessels. The atherosclerotic lesions in familial hypercholesterolaemia are mainly caused by pathogenic variants of the low-density lipoprotein receptor (LDLR) gene, which plays an important role in cholesterol metabolism. Normally, cholesterol-laden low-density lipoproteins bind to the LDLR receptor on the surface of liver cells to be removed from the bloodstream by internalisation with hepatocytes. In familial hypercholesterolaemia, the function of the receptor is impaired and the uptake of low-density lipoproteins is significantly reduced. As a result, cholesterol accumulates in the subendothelial space on the inner wall of blood vessels, triggering atherogenesis, the formation of atherosclerotic plaques. At present, there are no effective and universal approaches to the diagnosis and treatment of familial hypercholesterolaemia. A relevant approach to study the molecular genetic mechanisms of the disease and to obtain systems for screening chemical compounds as potential drugs is the generation of cellular models based on patient-specific induced pluripotent stem cells. The aim of our work was to derive an isogenic genetically modified induced pluripotent stem cell line by correcting the pathogenic allelic variant c.530C of the LDLR gene in the original iPSC previously obtained from a compound heterozygote patient with familial hypercholesterolaemia. The resulting isogenic iPSC line differs from the original by only one corrected nucleotide substitution, allowing us to study the direct effect of this pathogenic genetic variant on physiological changes in relevant differentiated cells. CRISPR/Cas-mediated base editing was used to correct the single nucleotide substitution. The resulting genetically modified iPSC line has pluripotency traits, a normal karyotype, a set of short tandem repeats identical to that in the original line and can be used to obtain differentiated derivatives necessary for the elaboration of relevant cell models. |
| format | Article |
| id | doaj-art-a94eec5fc8a1428c950d68173c1a7f09 |
| institution | Matheson Library |
| issn | 2500-3259 |
| language | English |
| publishDate | 2025-04-01 |
| 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-a94eec5fc8a1428c950d68173c1a7f092025-08-04T14:11:43ZengSiberian 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 селекции2500-32592025-04-0129218919910.18699/vjgb-25-221556Isogenic induced pluripotent stem cell line ICGi036-A-1 from a patient with familial hypercholesterolaemia, derived by correcting a pathogenic variant of the gene LDLR c.530C>TA. S. Zueva0A. I. Shevchenko1S. P. Medvedev2E. A. Elisaphenko3A. A. Sleptcov4M. S. Nazarenko5N. A. Tmoyan6S. M. Zakian7I. S. Zakharova8Institute 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 SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; National Medical Research Center of Cardiology named after academician E.I. ChazovInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesFamilial hypercholesterolaemia is a common monogenic disorder characterized by high plasma cholesterol levels leading to chronic cardiovascular disease with high risk and often early manifestation due to atherosclerotic lesions of the blood vessels. The atherosclerotic lesions in familial hypercholesterolaemia are mainly caused by pathogenic variants of the low-density lipoprotein receptor (LDLR) gene, which plays an important role in cholesterol metabolism. Normally, cholesterol-laden low-density lipoproteins bind to the LDLR receptor on the surface of liver cells to be removed from the bloodstream by internalisation with hepatocytes. In familial hypercholesterolaemia, the function of the receptor is impaired and the uptake of low-density lipoproteins is significantly reduced. As a result, cholesterol accumulates in the subendothelial space on the inner wall of blood vessels, triggering atherogenesis, the formation of atherosclerotic plaques. At present, there are no effective and universal approaches to the diagnosis and treatment of familial hypercholesterolaemia. A relevant approach to study the molecular genetic mechanisms of the disease and to obtain systems for screening chemical compounds as potential drugs is the generation of cellular models based on patient-specific induced pluripotent stem cells. The aim of our work was to derive an isogenic genetically modified induced pluripotent stem cell line by correcting the pathogenic allelic variant c.530C of the LDLR gene in the original iPSC previously obtained from a compound heterozygote patient with familial hypercholesterolaemia. The resulting isogenic iPSC line differs from the original by only one corrected nucleotide substitution, allowing us to study the direct effect of this pathogenic genetic variant on physiological changes in relevant differentiated cells. CRISPR/Cas-mediated base editing was used to correct the single nucleotide substitution. The resulting genetically modified iPSC line has pluripotency traits, a normal karyotype, a set of short tandem repeats identical to that in the original line and can be used to obtain differentiated derivatives necessary for the elaboration of relevant cell models.https://vavilov.elpub.ru/jour/article/view/4537familial hypercholesterolaemialdlrinduced pluripotent stem cellsgenome editingisogenic cell lines |
| spellingShingle | A. S. Zueva A. I. Shevchenko S. P. Medvedev E. A. Elisaphenko A. A. Sleptcov M. S. Nazarenko N. A. Tmoyan S. M. Zakian I. S. Zakharova Isogenic induced pluripotent stem cell line ICGi036-A-1 from a patient with familial hypercholesterolaemia, derived by correcting a pathogenic variant of the gene LDLR c.530C>T Вавиловский журнал генетики и селекции familial hypercholesterolaemia ldlr induced pluripotent stem cells genome editing isogenic cell lines |
| title | Isogenic induced pluripotent stem cell line ICGi036-A-1 from a patient with familial hypercholesterolaemia, derived by correcting a pathogenic variant of the gene LDLR c.530C>T |
| title_full | Isogenic induced pluripotent stem cell line ICGi036-A-1 from a patient with familial hypercholesterolaemia, derived by correcting a pathogenic variant of the gene LDLR c.530C>T |
| title_fullStr | Isogenic induced pluripotent stem cell line ICGi036-A-1 from a patient with familial hypercholesterolaemia, derived by correcting a pathogenic variant of the gene LDLR c.530C>T |
| title_full_unstemmed | Isogenic induced pluripotent stem cell line ICGi036-A-1 from a patient with familial hypercholesterolaemia, derived by correcting a pathogenic variant of the gene LDLR c.530C>T |
| title_short | Isogenic induced pluripotent stem cell line ICGi036-A-1 from a patient with familial hypercholesterolaemia, derived by correcting a pathogenic variant of the gene LDLR c.530C>T |
| title_sort | isogenic induced pluripotent stem cell line icgi036 a 1 from a patient with familial hypercholesterolaemia derived by correcting a pathogenic variant of the gene ldlr c 530c t |
| topic | familial hypercholesterolaemia ldlr induced pluripotent stem cells genome editing isogenic cell lines |
| url | https://vavilov.elpub.ru/jour/article/view/4537 |
| work_keys_str_mv | AT aszueva isogenicinducedpluripotentstemcelllineicgi036a1fromapatientwithfamilialhypercholesterolaemiaderivedbycorrectingapathogenicvariantofthegeneldlrc530ct AT aishevchenko isogenicinducedpluripotentstemcelllineicgi036a1fromapatientwithfamilialhypercholesterolaemiaderivedbycorrectingapathogenicvariantofthegeneldlrc530ct AT spmedvedev isogenicinducedpluripotentstemcelllineicgi036a1fromapatientwithfamilialhypercholesterolaemiaderivedbycorrectingapathogenicvariantofthegeneldlrc530ct AT eaelisaphenko isogenicinducedpluripotentstemcelllineicgi036a1fromapatientwithfamilialhypercholesterolaemiaderivedbycorrectingapathogenicvariantofthegeneldlrc530ct AT aasleptcov isogenicinducedpluripotentstemcelllineicgi036a1fromapatientwithfamilialhypercholesterolaemiaderivedbycorrectingapathogenicvariantofthegeneldlrc530ct AT msnazarenko isogenicinducedpluripotentstemcelllineicgi036a1fromapatientwithfamilialhypercholesterolaemiaderivedbycorrectingapathogenicvariantofthegeneldlrc530ct AT natmoyan isogenicinducedpluripotentstemcelllineicgi036a1fromapatientwithfamilialhypercholesterolaemiaderivedbycorrectingapathogenicvariantofthegeneldlrc530ct AT smzakian isogenicinducedpluripotentstemcelllineicgi036a1fromapatientwithfamilialhypercholesterolaemiaderivedbycorrectingapathogenicvariantofthegeneldlrc530ct AT iszakharova isogenicinducedpluripotentstemcelllineicgi036a1fromapatientwithfamilialhypercholesterolaemiaderivedbycorrectingapathogenicvariantofthegeneldlrc530ct |