vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/vjgb-25-22vavilov-4537Research ArticleКЛЕТОЧНАЯ БИОЛОГИЯCELL BIOLOGYИзогенная линия индуцированных плюрипотентных стволовых клеток ICGi036-A-1 от пациента с семейной гиперхолестеринемией, созданная путем коррекции патогенного варианта гена LDLR c.530C>TIsogenic 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>TЗуеваА. С.ZuevaA. S.

Новосибирск

Novosibirsk

ШевченкоА. И.ShevchenkoA. I.

Новосибирск

Novosibirsk

МедведевС. П.MedvedevS. P.

Новосибирск

Novosibirsk

ЕлисафенкоЕ. А.ElisaphenkoE. A.

Новосибирск

Novosibirsk

СлепцовА. А.SleptcovA. A.

Новосибирск; Томск

Novosibirsk; Tomsk

НазаренкоМ. С.NazarenkoM. S.

Новосибирск; Томск

Novosibirsk; Tomsk

ТмоянН. А.TmoyanN. A.

Новосибирск;Москва

Novosibirsk; Moscow

ЗакиянС. М.ZakianS. M.

Новосибирск

Novosibirsk

ЗахароваИ. С.ZakharovaI. S.

Новосибирск

Novosibirsk

zakharova@bionet.nsc.ruФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Новосибирский национальный исследовательский государственный университетРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State UniversityRussian FederationФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наукРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesRussian FederationФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Научно-исследовательский институт медицинской генетики, Томский национальный исследовательский медицинский центр Российской академии наукРоссияInstitute 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 SciencesRussian FederationФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук;Национальный медицинский исследовательский центр кардиологии имени академика Е.И. Чазова Министерства здравоохранения Российской ФедерацииРоссияInstitute 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. ChazovRussian Federation202510042025292189199Copyright © Зуева А.С., Шевченко А.И., Медведев С.П., Елисафенко Е.А., Слепцов А.А., Назаренко М.С., Тмоян Н.А., Закиян С.М., Захарова И.С., 20252025Зуева А.С., Шевченко А.И., Медведев С.П., Елисафенко Е.А., Слепцов А.А., Назаренко М.С., Тмоян Н.А., Закиян С.М., Захарова И.С.Zueva A.S., Shevchenko A.I., Medvedev S.P., Elisaphenko E.A., Sleptcov A.A., Nazarenko M.S., Tmoyan N.A., Zakian S.M., Zakharova I.S.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/4537

Семейная гиперхолестеринемия является распространенным моногенным заболеванием, которое характеризуется повышенным содержанием холестерина в плазме крови, приводящим к хроническим заболеваниям сердечно-сосудистой системы с высоким риском и ранним проявлением развития патологий, вызванных атеросклеротическими поражениями кровеносных сосудов. Образование атеросклеротических бляшек при семейной гиперхолестеринемии в основном обусловлено патогенными вариантами гена рецептора липопротеинов низкой плотности LDLR (low-density lipoprotein receptor), играющего важную роль в метаболизме холестерина. В норме липопротеины низкой плотности, переносящие холестерин, связываются с рецептором LDLR на поверхности клеток печени и выводятся из кровотока путем интернализации гепатоцитами. При семейной гиперхолестеринемии происходит нарушение функционирования рецептора и значительное снижение интернализации липопротеинов низкой плотности. Это приводит к их накоплению в субэндотелиальном пространстве внутренней стенки кровеносных сосудов и вызывает атерогенез – образование атеросклеротических бляшек. На сегодняшний день не существует эффективных и универсальных подходов к диагностике и лечению семейной гиперхолестеринемии. Актуальным подходом для исследования молекулярно-генетических особенностей заболевания и разработки систем скрининга химических соединений – потенциальных лекарственных препаратов – является создание клеточных моделей на основе индуцированных плюрипотентных стволовых клеток (ИПСК) пациентов. Целью нашей работы было создание изогенной генетически модифицированной линии индуцированных плюрипотентных стволовых клеток путем коррекции патогенного аллельного варианта c.530C гена LDLR в линии ИПСК, полученной ранее от пациента-компаундной гетерозиготы с семейной гиперхолестеринемией. Созданная изогенная клеточная линия ИПСК отличается от исходной только одной скорректированной нуклеотидной заменой, что позволяет исследовать непосредственное влияние данного патогенного генетического варианта на физиологические изменения в релевантных дифференцированных клетках. Для коррекции однонуклеотидных замен использован CRISPR/Cas9-опосредованный метод редактирования оснований. Полученная генетически модифицированная линия ИПСК обладает свойствами плюрипотентности, имеет нормальный кариотип, идентичный исходной линии набор коротких тандемных повторов и может быть использована для формирования дифференцированных производных, необходимых при разработке релевантных клеточных моделей.

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.

семейная гиперхолестеринемияLDLRиндуцированные плюрипотентные стволовые клеткигеномное редактированиеизогенные линии клетокfamilial hypercholesterolaemiaLDLRinduced pluripotent stem cellsgenome editingisogenic cell linesThe work was supported by the Russian Science Foundation grant No. 24-15-00346, https://rscf.ru/project/ 24-15-00346/.ReferencesBauer D.E., Canver M.C., Orkin S.H. Generation of genomic deletions in mammalian cell lines via CRISPR/Cas9. J Vis Exp. 2015; 95:e52118. doi 10.3791/52118Bauer D.E., Canver M.C., Orkin S.H. Generation of genomic deletions in mammalian cell lines via CRISPR/Cas9. J Vis Exp. 2015; 95:e52118. doi 10.3791/52118Bonnycastle L.L., Swift A.J., Mansell E.C., Lee A., Winnicki E., Li E.S., Robertson C.C., Parsons V.A., Huynh T., Krilow C., Mohlke K.L., Erdos M.R., Narisu N., Collins F.S. Generation of human isogenic induced pluripotent stem cell lines with CRISPR prime editing. Cris J. 2024;7(1):53-67. doi 10.1089/crispr.2023.0066Bonnycastle L.L., Swift A.J., Mansell E.C., Lee A., Winnicki E., Li E.S., Robertson C.C., Parsons V.A., Huynh T., Krilow C., Mohlke K.L., Erdos M.R., Narisu N., Collins F.S. Generation of human isogenic induced pluripotent stem cell lines with CRISPR prime editing. Cris J. 2024;7(1):53-67. doi 10.1089/crispr.2023.0066Bourbon M., Alves A.C., Medeiros A.M., Silva S., Soutar A.K. Familial hypercholesterolaemia in Portugal. Atherosclerosis. 2008; 196(2):633-642. doi 10.1016/j.atherosclerosis.2007.07.019Bourbon M., Alves A.C., Medeiros A.M., Silva S., Soutar A.K. Familial hypercholesterolaemia in Portugal. Atherosclerosis. 2008; 196(2):633-642. doi 10.1016/j.atherosclerosis.2007.07.019Brooks I.R., Garrone C.M., Kerins C., Kiar C.S., Syntaka S., Xu J.Z., Spagnoli F.M., Watt F.M. Functional genomics and the future of iPSCs in disease modeling. Stem Cell Rep. 2022;17(5):1033-1047. doi 10.1016/j.stemcr.2022.03.019Brooks I.R., Garrone C.M., Kerins C., Kiar C.S., Syntaka S., Xu J.Z., Spagnoli F.M., Watt F.M. Functional genomics and the future of iPSCs in disease modeling. Stem Cell Rep. 2022;17(5):1033-1047. doi 10.1016/j.stemcr.2022.03.019Cerneckis J., Cai H., Shi Y. Induced pluripotent stem cells (iPSCs): molecular mechanisms of induction and applications. Signal Transduct Target Ther. 2024;9(1):112. doi 10.1038/s41392-024-01809-0Cerneckis J., Cai H., Shi Y. Induced pluripotent stem cells (iPSCs): molecular mechanisms of induction and applications. Signal Transduct Target Ther. 2024;9(1):112. doi 10.1038/s41392-024-01809-0Chai A.C., Cui M., Chemello F., Li H., Chen K., Tan W., Atmanli A., McAnally J.R., Zhang Y., Xu L., Liu N., Bassel-Duby R., Olson E.N. Base editing correction of hypertrophic cardiomyopathy in human cardiomyocytes and humanized mice. Nat Med. 2023;29(2):401- 411. doi 10.1038/s41591-022-02176-5Chai A.C., Cui M., Chemello F., Li H., Chen K., Tan W., Atmanli A., McAnally J.R., Zhang Y., Xu L., Liu N., Bassel-Duby R., Olson E.N. Base editing correction of hypertrophic cardiomyopathy in human cardiomyocytes and humanized mice. Nat Med. 2023;29(2):401- 411. doi 10.1038/s41591-022-02176-5Choppa P.C., Vojdani A., Tagle C., Andrin R., Magtoto L. 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;12(5):301-308. doi 10.1006/mcpr.1998.0186Choppa P.C., Vojdani A., Tagle C., Andrin R., Magtoto L. 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;12(5):301-308. doi 10.1006/mcpr.1998.0186Cowan C.A., Klimanskaya I., McMahon J., Atienza J., Witmyer J., Zucker J.P., Wang S., Morton C.C., McMahon A.P., Powers D., Melton D.A. Derivation of embryonic stem-cell lines from human blastocysts. N Engl J Med. 2004;350(13):1353-1356. doi 10.1056/nejmsr040330Cowan C.A., Klimanskaya I., McMahon J., Atienza J., Witmyer J., Zucker J.P., Wang S., Morton C.C., McMahon A.P., Powers D., Melton D.A. Derivation of embryonic stem-cell lines from human blastocysts. N Engl J Med. 2004;350(13):1353-1356. doi 10.1056/nejmsr040330Ezhov M.V., Bazhan S.S., Ershova A.I., Meshkov A.N., Sokolov A.A., Kukharchuk V.V., Gurevich V.S., Voevoda M.I., Sergienko I.V., Shakhtshneider E.V., Pokrovsky S.N., Konovalov G.A., Leontyeva I.V., Konstantinov V.O., Shcherbakova M.Yu., Zakharova I.N., Balakhonova T.V., Filippov A.E., Akhmedzhanov N.M., Aleksandrova O.Yu., Lipovetsky B.M. Clinical guidelines for familial hypercholesterolemia. Ateroscleroz. 2019;15(1):58-98 (in Russian)Ezhov M.V., Bazhan S.S., Ershova A.I., Meshkov A.N., Sokolov A.A., Kukharchuk V.V., Gurevich V.S., Voevoda M.I., Sergienko I.V., Shakhtshneider E.V., Pokrovsky S.N., Konovalov G.A., Leontyeva I.V., Konstantinov V.O., Shcherbakova M.Yu., Zakharova I.N., Balakhonova T.V., Filippov A.E., Akhmedzhanov N.M., Aleksandrova O.Yu., Lipovetsky B.M. Clinical guidelines for familial hypercholesterolemia. Ateroscleroz. 2019;15(1):58-98 (in Russian)Ference B.A., Ginsberg H.N., Graham I., Ray K.K., Packard C.J., Bruckert E., Hegele R.A., Krauss R.M., Raal F.J., Schunkert H., Watt G.F., Borén J., Fazio S., Horton J.D., Masana L., Nicholls S.J., Nordestgaard B.G., Van De Sluis B., Taskinen M.R., Tokgözoǧlu L., Landmesser U., Laufs U., Wiklund O., Stock J.K., Chapman M.J., Catapano A.L. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017;38(32):2459- 2472. doi 10.1093/eurheartj/ehx144Ference B.A., Ginsberg H.N., Graham I., Ray K.K., Packard C.J., Bruckert E., Hegele R.A., Krauss R.M., Raal F.J., Schunkert H., Watt G.F., Borén J., Fazio S., Horton J.D., Masana L., Nicholls S.J., Nordestgaard B.G., Van De Sluis B., Taskinen M.R., Tokgözoǧlu L., Landmesser U., Laufs U., Wiklund O., Stock J.K., Chapman M.J., Catapano A.L. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017;38(32):2459- 2472. doi 10.1093/eurheartj/ehx144Fularski P., Hajdys J., Majchrowicz G., Stabrawa M., Młynarska E., Rysz J., Franczyk B. Unveiling familial hypercholesterolemia – review, cardiovascular complications, lipid-lowering treatment and its efficacy. Int J Mol Sci. 2024;25(3):1637. doi 10.3390/ijms25031637Fularski P., Hajdys J., Majchrowicz G., Stabrawa M., Młynarska E., Rysz J., Franczyk B. Unveiling familial hypercholesterolemia – review, cardiovascular complications, lipid-lowering treatment and its efficacy. Int J Mol Sci. 2024;25(3):1637. doi 10.3390/ijms25031637Gaudelli N.M., Komor A.C., Rees H.A., Packer M.S., Badran A.H., Bryson D.I., Liu D.R. Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage. Nature. 2017;551(7681): 464-471. doi 10.1038/nature24644Gaudelli N.M., Komor A.C., Rees H.A., Packer M.S., Badran A.H., Bryson D.I., Liu D.R. Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage. Nature. 2017;551(7681): 464-471. doi 10.1038/nature24644Grigor’eva E.V., Malakhova A.A., Yarkova E.S., Minina J.M., Vyatkin Y.V., Nadtochy J.A., Khabarova E.A., Rzaev J.A., Medvedev S.P., Zakian S.M. Generation and characterization of two induced pluripotent stem cell lines (ICGi052-A and ICGi052-B) from a patient with frontotemporal dementia with parkinsonism-17 associated with the pathological variant c.2013T>G in the MAPT gene. Vavilovskii Zhurnal Genetiki i Selektsii = Vavilov J Genet Breed. 2024;28(7):679-687. doi 10.18699/vjgb-24-76Grigor’eva E.V., Malakhova A.A., Yarkova E.S., Minina J.M., Vyatkin Y.V., Nadtochy J.A., Khabarova E.A., Rzaev J.A., Medvedev S.P., Zakian S.M. Generation and characterization of two induced pluripotent stem cell lines (ICGi052-A and ICGi052-B) from a patient with frontotemporal dementia with parkinsonism-17 associated with the pathological variant c.2013T>G in the MAPT gene. Vavilovskii Zhurnal Genetiki i Selektsii = Vavilov J Genet Breed. 2024;28(7):679-687. doi 10.18699/vjgb-24-76Gu J., Gupta R.N., Cheng H.K., Xu Y., Raal F.J. Current treatments for the management of homozygous familial hypercholesterolaemia: a systematic review and commentary. Eur J Prev Cardiol. 2024; 31(15):1833-1849. doi 10.1093/eurjpc/zwae144Gu J., Gupta R.N., Cheng H.K., Xu Y., Raal F.J. Current treatments for the management of homozygous familial hypercholesterolaemia: a systematic review and commentary. Eur J Prev Cardiol. 2024; 31(15):1833-1849. doi 10.1093/eurjpc/zwae144Harada-Shiba M. Impact of familial hypercholesterolemia diagnosis in real-world data. J Atheroscler Thromb. 2023;30(10):1303. doi 10.5551/jat.ED241Harada-Shiba M. Impact of familial hypercholesterolemia diagnosis in real-world data. J Atheroscler Thromb. 2023;30(10):1303. doi 10.5551/jat.ED241Hendricks-Sturrup R.M., Clark-Locascio J., Lu C.Y. A global review on the utility of genetic testing for familial hypercholesterolemia. J Pers Med. 2020;10(2):23. doi 10.3390/pm10020023Hendricks-Sturrup R.M., Clark-Locascio J., Lu C.Y. A global review on the utility of genetic testing for familial hypercholesterolemia. J Pers Med. 2020;10(2):23. doi 10.3390/pm10020023Hofer M., Lutolf M.P. Engineering organoids. Nat Rev Mater. 2021; 6(5):402-420. doi 10.1038/s41578-021-00279-yHofer M., Lutolf M.P. Engineering organoids. Nat Rev Mater. 2021; 6(5):402-420. doi 10.1038/s41578-021-00279-yHopkins P.N., Toth P.P., Ballantyne C.M., Rader D.J. Familial hypercholesterolemias: prevalence, genetics, diagnosis and screening recommendations from the national lipid association expert panel on familial hypercholesterolemia. J Clin Lipidol. 2011;5(3):S9. doi 10.1016/j.jacl.2011.03.452Hopkins P.N., Toth P.P., Ballantyne C.M., Rader D.J. Familial hypercholesterolemias: prevalence, genetics, diagnosis and screening recommendations from the national lipid association expert panel on familial hypercholesterolemia. J Clin Lipidol. 2011;5(3):S9. doi 10.1016/j.jacl.2011.03.452Hu J.H., Miller S.M., Geurts M.H., Tang W., Chen L., Sun N., Zeina C.M., Gao X., Rees H.A., Lin Z., Liu D.R. Evolved Cas9 variants with broad PAM compatibility and high DNA specificity. Nature. 2018;556(7699):57-63. doi 10.1038/nature26155Hu J.H., Miller S.M., Geurts M.H., Tang W., Chen L., Sun N., Zeina C.M., Gao X., Rees H.A., Lin Z., Liu D.R. Evolved Cas9 variants with broad PAM compatibility and high DNA specificity. Nature. 2018;556(7699):57-63. doi 10.1038/nature26155Huang C.C., Niu D.M., Charng M.J. Genetic analysis in a Taiwanese cohort of 750 index patients with clinically diagnosed familial hypercholesterolemia. J Atheroscler Thromb. 2022;29(5):639-653. doi 10.5551/jat.62773Huang C.C., Niu D.M., Charng M.J. Genetic analysis in a Taiwanese cohort of 750 index patients with clinically diagnosed familial hypercholesterolemia. J Atheroscler Thromb. 2022;29(5):639-653. doi 10.5551/jat.62773Jannes C.E., Santos R.D., de Souza Silva P.R., Turolla L., GagliardiA.C.M., Marsiglia J.D.C., ChacraA.P., Miname M.H., Rocha V.Z., Filho W.S., Krieger J.E., Pereira A.C. Familial hypercholesterolemia in Brazil: cascade screening program, clinical and genetic aspects. Atherosclerosis. 2015;238(1):101-107. doi 10.1016/j.atherosclerosis.2014.11.009Jannes C.E., Santos R.D., de Souza Silva P.R., Turolla L., GagliardiA.C.M., Marsiglia J.D.C., ChacraA.P., Miname M.H., Rocha V.Z., Filho W.S., Krieger J.E., Pereira A.C. Familial hypercholesterolemia in Brazil: cascade screening program, clinical and genetic aspects. Atherosclerosis. 2015;238(1):101-107. doi 10.1016/j.atherosclerosis.2014.11.009Kannan S., Farid M., Lin B.L., Miyamoto M., Kwon C. Transcriptomic entropy benchmarks stem cell-derived cardiomyocyte maturation against endogenous tissue at single cell level. PLoS Comput Biol. 2021;17(9):e1009305. doi 10.1371/journal.pcbi.1009305Kannan S., Farid M., Lin B.L., Miyamoto M., Kwon C. Transcriptomic entropy benchmarks stem cell-derived cardiomyocyte maturation against endogenous tissue at single cell level. PLoS Comput Biol. 2021;17(9):e1009305. doi 10.1371/journal.pcbi.1009305Kawatani K., Nambara T., Nawa N., Yoshimatsu H., Kusakabe H., Hirata K., Tanave A., Sumiyama K., Banno K., Taniguchi H., Arahori H., Ozono K., Kitabatake Y. A human isogenic iPSC-derived cell line panel identifies major regulators of aberrant astrocyte proliferation in Down syndrome. Commun Biol. 2021;4(1):730. doi 10.1038/s42003-021-02242-7Kawatani K., Nambara T., Nawa N., Yoshimatsu H., Kusakabe H., Hirata K., Tanave A., Sumiyama K., Banno K., Taniguchi H., Arahori H., Ozono K., Kitabatake Y. A human isogenic iPSC-derived cell line panel identifies major regulators of aberrant astrocyte proliferation in Down syndrome. Commun Biol. 2021;4(1):730. doi 10.1038/s42003-021-02242-7Koblan L.W., Erdos M.R., Wilson C., Cabral W.A., Levy J.M., Xiong Z.M., Tavarez U.L., Davison L.M., Gete Y.G., Mao X., Newby G.A., Doherty S.P., Narisu N., Sheng Q., Krilow C., Lin C.Y., Gordon L.B., Cao K., Collins F.S., Brown J.D., Liu D.R. In vivo base editing rescues Hutchinson-Gilford progeria syndrome in mice. Nature. 2021;589(7843):608-614. doi 10.1038/s41586-020-03086-7Koblan L.W., Erdos M.R., Wilson C., Cabral W.A., Levy J.M., Xiong Z.M., Tavarez U.L., Davison L.M., Gete Y.G., Mao X., Newby G.A., Doherty S.P., Narisu N., Sheng Q., Krilow C., Lin C.Y., Gordon L.B., Cao K., Collins F.S., Brown J.D., Liu D.R. In vivo base editing rescues Hutchinson-Gilford progeria syndrome in mice. Nature. 2021;589(7843):608-614. doi 10.1038/s41586-020-03086-7Komor A.C., Kim Y.B., Packer M.S., Zuris J.A., Liu D.R. Programmable editing of a target base in genomic DNA without doublestranded DNA cleavage. Nature. 2016;533(7603):420-424. doi 10.1038/nature17946Komor A.C., Kim Y.B., Packer M.S., Zuris J.A., Liu D.R. Programmable editing of a target base in genomic DNA without doublestranded DNA cleavage. Nature. 2016;533(7603):420-424. doi 10.1038/nature17946Lawlor K.T., Vanslambrouck J.M., Higgins J.W., Chambon A., Bishard K., Arndt D., Er P.X., Wilson S.B., Howden S.E., Tan K.S., Li F., Hale L.J., Shepherd B., Pentoney S., Presnell S.C., Chen A.E., Little M.H. Cellular extrusion bioprinting improves kidney organoid reproducibility and conformation. Nat Mater. 2021;20(2):260-271. doi 10.1038/s41563-020-00853-9Lawlor K.T., Vanslambrouck J.M., Higgins J.W., Chambon A., Bishard K., Arndt D., Er P.X., Wilson S.B., Howden S.E., Tan K.S., Li F., Hale L.J., Shepherd B., Pentoney S., Presnell S.C., Chen A.E., Little M.H. Cellular extrusion bioprinting improves kidney organoid reproducibility and conformation. Nat Mater. 2021;20(2):260-271. doi 10.1038/s41563-020-00853-9Liang Y., Sun X., Duan C., Zhou Y., Cui Z., Ding C., Gu J., Mao S., Ji S., Chan H.F., Tang S., Chen J. Generation of a gene-corrected human iPSC line (CSUASOi004-A-1) from a retinitis pigmentosa patient with heterozygous c.2699G>A mutation in the PRPF6 gene. Stem Cell Res. 2022;64:103572. doi 10.1016/j.scr.2022.102911Liang Y., Sun X., Duan C., Zhou Y., Cui Z., Ding C., Gu J., Mao S., Ji S., Chan H.F., Tang S., Chen J. Generation of a gene-corrected human iPSC line (CSUASOi004-A-1) from a retinitis pigmentosa patient with heterozygous c.2699G>A mutation in the PRPF6 gene. Stem Cell Res. 2022;64:103572. doi 10.1016/j.scr.2022.102911Malakhova A.A., Grigor’eva E.V., Pavlova S.V., Malankhanova T.B., Valetdinova K.R., Vyatkin Y.V., Khabarova E.A., Rzaev J.A., Zakian S.M., Medvedev S.P. Generation of induced pluripotent stem cell lines ICGi021-A and ICGi022-A from peripheral blood mononuclear cells of two healthy individuals from Siberian population. Stem Cell Res. 2020;48:101952. doi 10.1016/j.scr.2020.101952Malakhova A.A., Grigor’eva E.V., Pavlova S.V., Malankhanova T.B., Valetdinova K.R., Vyatkin Y.V., Khabarova E.A., Rzaev J.A., Zakian S.M., Medvedev S.P. Generation of induced pluripotent stem cell lines ICGi021-A and ICGi022-A from peripheral blood mononuclear cells of two healthy individuals from Siberian population. Stem Cell Res. 2020;48:101952. doi 10.1016/j.scr.2020.101952Meshkov A., Ershova A., Kiseleva A., Zotova E., Sotnikova E., Petukhova A., Zharikova A., Malyshev P., Rozhkova T., Blokhina A., Limonova A., Ramensky V., Divashuk M., Khasanova Z., Bukaeva A., Kurilova O., Skirko O., Pokrovskaya M., Mikova V., Snigir E., Akinshina A., Mitrofanov S., Kashtanova D., Makarov V., Kukharchuk V., Boytsov S., Yudin S., Drapkina O. The LDLR, APOB, and PCSK9 variants of index patients with familial hypercholesterolemia in Russia. Genes. 2021;12(1):66. doi 10.3390/genes12010066Meshkov A., Ershova A., Kiseleva A., Zotova E., Sotnikova E., Petukhova A., Zharikova A., Malyshev P., Rozhkova T., Blokhina A., Limonova A., Ramensky V., Divashuk M., Khasanova Z., Bukaeva A., Kurilova O., Skirko O., Pokrovskaya M., Mikova V., Snigir E., Akinshina A., Mitrofanov S., Kashtanova D., Makarov V., Kukharchuk V., Boytsov S., Yudin S., Drapkina O. The LDLR, APOB, and PCSK9 variants of index patients with familial hypercholesterolemia in Russia. Genes. 2021;12(1):66. doi 10.3390/genes12010066Mohd Nor N.S., Al-Khateeb A.M., Chua Y.A., Mohd Kasim N.A., Mohd Nawawi H. Heterozygous familial hypercholesterolaemia in a pair of identical twins: a case report and updated review. BMC Pediatr. 2019;19(1):106. doi 10.1186/S12887-019-1474-y/tables/2Mohd Nor N.S., Al-Khateeb A.M., Chua Y.A., Mohd Kasim N.A., Mohd Nawawi H. Heterozygous familial hypercholesterolaemia in a pair of identical twins: a case report and updated review. BMC Pediatr. 2019;19(1):106. doi 10.1186/S12887-019-1474-y/tables/2Nandy K., Babu D., Rani S., Joshi G., Ijee S., George A., Palani D., Premkumar C., Rajesh P., Vijayanand S., David E., Murugesan M., Velayudhan S.R. Efficient gene editing in induced pluripotent stem cells enabled by an inducible adenine base editor with tunable expression. Sci Rep. 2023;13(1):21953. doi 10.1038/s41598-023-42174-2Nandy K., Babu D., Rani S., Joshi G., Ijee S., George A., Palani D., Premkumar C., Rajesh P., Vijayanand S., David E., Murugesan M., Velayudhan S.R. Efficient gene editing in induced pluripotent stem cells enabled by an inducible adenine base editor with tunable expression. Sci Rep. 2023;13(1):21953. doi 10.1038/s41598-023-42174-2Nazarenko M.S., Sleptcov A.A., Zarubin A.A., Salakhov R.R., Shevchenko A.I., Tmoyan N.A., Elisaphenko E.A., Zubkova E.S., Zheltysheva N.V., Ezhov M.V., Kukharchuk V.V., Parfyonova Y.V., Zakian S.M., Zakharova I.S. Calling and phasing of single-nucleotide and structural variants of the LDLR gene using Oxford Nano- pore MinION. Int J Mol Sci. 2023;24(5):4471. doi 10.3390/ijms24054471Nazarenko M.S., Sleptcov A.A., Zarubin A.A., Salakhov R.R., Shevchenko A.I., Tmoyan N.A., Elisaphenko E.A., Zubkova E.S., Zheltysheva N.V., Ezhov M.V., Kukharchuk V.V., Parfyonova Y.V., Zakian S.M., Zakharova I.S. Calling and phasing of single-nucleotide and structural variants of the LDLR gene using Oxford Nano- pore MinION. Int J Mol Sci. 2023;24(5):4471. doi 10.3390/ijms24054471Newby G.A., Yen J.S., Woodard K.J., Mayuranathan T., Lazzarotto C.R., Li Y., Sheppard-Tillman H., Porter S.N., Yao Y., Mayberry K., Everette K.A., Jang Y., Podracky C.J., Thaman E., Lechauve C., Sharma A., Henderson J.M., Richter M.F., Zhao K.T., Miller S.M., Wang T., Koblan L.W., McCaffrey A.P., Tisdale J.F., Kalfa T.A., Pruett-Miller S.M., Tsai S.Q., Weiss M.J., Liu D.R. Base editing of haematopoietic stem cells rescues sickle cell disease in mice. Nature. 2021;595(7866):295-302. doi 10.1038/S41586-021-03609-wNewby G.A., Yen J.S., Woodard K.J., Mayuranathan T., Lazzarotto C.R., Li Y., Sheppard-Tillman H., Porter S.N., Yao Y., Mayberry K., Everette K.A., Jang Y., Podracky C.J., Thaman E., Lechauve C., Sharma A., Henderson J.M., Richter M.F., Zhao K.T., Miller S.M., Wang T., Koblan L.W., McCaffrey A.P., Tisdale J.F., Kalfa T.A., Pruett-Miller S.M., Tsai S.Q., Weiss M.J., Liu D.R. Base editing of haematopoietic stem cells rescues sickle cell disease in mice. Nature. 2021;595(7866):295-302. doi 10.1038/S41586-021-03609-wNiemitz E. Isogenic iPSC-derived models of disease. Nat Genet. 2014;46(1):7. doi 10.1038/ng.2864Niemitz E. Isogenic iPSC-derived models of disease. Nat Genet. 2014;46(1):7. doi 10.1038/ng.2864Okano H., Morimoto S. iPSC-based disease modeling and drug discovery in cardinal neurodegenerative disorders. Cell Stem Cell. 2022; 29(2):189-208. doi 10.1016/j.stem.2022.01.007Okano H., Morimoto S. iPSC-based disease modeling and drug discovery in cardinal neurodegenerative disorders. Cell Stem Cell. 2022; 29(2):189-208. doi 10.1016/j.stem.2022.01.007Okita K., Yamakawa T., Matsumura Y., Sato Y., Amano N., Watanabe A., Goshima N., Yamanaka S. An efficient nonviral method to generate integration-free human-induced pluripotent stem cells from cord blood and peripheral blood cells. Stem Cells. 2013;31(3): 458-466. doi 10.1002/stem.1293Okita K., Yamakawa T., Matsumura Y., Sato Y., Amano N., Watanabe A., Goshima N., Yamanaka S. An efficient nonviral method to generate integration-free human-induced pluripotent stem cells from cord blood and peripheral blood cells. Stem Cells. 2013;31(3): 458-466. doi 10.1002/stem.1293Omer L., Hudson E.A., Zheng S., Hoying J.B., Shan Y., Boyd N.L. CRISPR correction of a homozygous low-density lipoprotein receptor mutation in familial hypercholesterolemia induced pluripotent stem cells. Hepatol Commun. 2017;1(9):886-898. doi 10.1002/hep4.1110Omer L., Hudson E.A., Zheng S., Hoying J.B., Shan Y., Boyd N.L. CRISPR correction of a homozygous low-density lipoprotein receptor mutation in familial hypercholesterolemia induced pluripotent stem cells. Hepatol Commun. 2017;1(9):886-898. doi 10.1002/hep4.1110Palacios L., Grandoso L., Cuevas N., Olano-Martín E., Martinez A., Tejedor D., Stef M. Molecular characterization of familial hypercholesterolemia in Spain. Atherosclerosis. 2012;221(1):137-142. doi 10.1016/j.atherosclerosis.2011.12.021Palacios L., Grandoso L., Cuevas N., Olano-Martín E., Martinez A., Tejedor D., Stef M. Molecular characterization of familial hypercholesterolemia in Spain. Atherosclerosis. 2012;221(1):137-142. doi 10.1016/j.atherosclerosis.2011.12.021Pavlova S.V., Shayakhmetova L.S., Pronyaeva K.A., Shulgina A.E., Zakian S.M., Dementyeva E.V. Generation of induced pluripotent stem cell lines ICGi022-A-3, ICGi022-A-4, and ICGi022-A-5 with p.Asn515del mutation introduced in MYBPC3 using CRISPR/Cas9. Russ J Dev Biol. 2023;54:96-103. doi 10.1134/S1062360423010113Pavlova S.V., Shayakhmetova L.S., Pronyaeva K.A., Shulgina A.E., Zakian S.M., Dementyeva E.V. Generation of induced pluripotent stem cell lines ICGi022-A-3, ICGi022-A-4, and ICGi022-A-5 with p.Asn515del mutation introduced in MYBPC3 using CRISPR/Cas9. Russ J Dev Biol. 2023;54:96-103. doi 10.1134/S1062360423010113Porto E.M., Komor A.C., Slaymaker I.M., Yeo G.W. Base editing: advances and therapeutic opportunities. Nat Rev Drug Discov. 2020; 19(12):839-859. doi 10.1038/s41573-020-0084-6Porto E.M., Komor A.C., Slaymaker I.M., Yeo G.W. Base editing: advances and therapeutic opportunities. Nat Rev Drug Discov. 2020; 19(12):839-859. doi 10.1038/s41573-020-0084-6Ray K.K., Ference B.A., Séverin T., Blom D., Nicholls S.J., Shiba M.H., Almahmeed W., Alonso R., Daccord M., Ezhov M., Olmo R.F., Jankowski P., Lanas F., Mehta R., Puri R., Wong N.D., Wood D., Zhao D., Gidding S.S., Virani S.S., Lloyd-Jones D., Pinto F., Perel P., Santos R.D. World Heart Federation Cholesterol Roadmap 2022. Glob Heart. 2022;17(1):75. doi 10.5334/gh.1154Ray K.K., Ference B.A., Séverin T., Blom D., Nicholls S.J., Shiba M.H., Almahmeed W., Alonso R., Daccord M., Ezhov M., Olmo R.F., Jankowski P., Lanas F., Mehta R., Puri R., Wong N.D., Wood D., Zhao D., Gidding S.S., Virani S.S., Lloyd-Jones D., Pinto F., Perel P., Santos R.D. World Heart Federation Cholesterol Roadmap 2022. Glob Heart. 2022;17(1):75. doi 10.5334/gh.1154Ray K.K., Pillas D., Hadjiphilippou S., Khunti K., Seshasai S.R.K., Vallejo-Vaz A.J., Neasham D., Addison J. Premature morbidity and mortality associated with potentially undiagnosed familial hypercholesterolemia in the general population. Am J Prev Cardiol. 2023; 15:100580. doi 10.1016/j.ajpc.2023.100580Ray K.K., Pillas D., Hadjiphilippou S., Khunti K., Seshasai S.R.K., Vallejo-Vaz A.J., Neasham D., Addison J. Premature morbidity and mortality associated with potentially undiagnosed familial hypercholesterolemia in the general population. Am J Prev Cardiol. 2023; 15:100580. doi 10.1016/j.ajpc.2023.100580Renner H., Grabos M., Becker K.J., Kagermeier T.E., Wu J., Otto M., Peischard S., Zeuschner D., Tsytsyura Y., Disse P., Klingauf J., Leidel S.A., Seebohm G., Schöler H.R., Bruder J.M. A fully automated high-throughput workflow for 3D-based chemical screening in human midbrain organoids. eLife. 2020;9:e52904. doi 10.7554/eLife.52904Renner H., Grabos M., Becker K.J., Kagermeier T.E., Wu J., Otto M., Peischard S., Zeuschner D., Tsytsyura Y., Disse P., Klingauf J., Leidel S.A., Seebohm G., Schöler H.R., Bruder J.M. A fully automated high-throughput workflow for 3D-based chemical screening in human midbrain organoids. eLife. 2020;9:e52904. doi 10.7554/eLife.52904Rothgangl T., Dennis M.K., Lin P.J.C., Oka R., Witzigmann D., Villiger L., Qi W., Hruzova M., Kissling L., Lenggenhager D., Borrelli C., Egli S., Frey N., Bakker N., Walker J.A., Kadina A.P., Victorov D.V., Pacesa M., Kreutzer S., Kontarakis Z., Moor A., Jinek M., Weissman D., Stoffel M., van Boxtel R., Holden K., Pardi N., Thöny B., Häberle J., Tam Y.K., Semple S.C., Schwank G. In vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels. Nat Biotechnol. 2021;39(8):949-957. doi 10.1038/s41587-021-00933-4Rothgangl T., Dennis M.K., Lin P.J.C., Oka R., Witzigmann D., Villiger L., Qi W., Hruzova M., Kissling L., Lenggenhager D., Borrelli C., Egli S., Frey N., Bakker N., Walker J.A., Kadina A.P., Victorov D.V., Pacesa M., Kreutzer S., Kontarakis Z., Moor A., Jinek M., Weissman D., Stoffel M., van Boxtel R., Holden K., Pardi N., Thöny B., Häberle J., Tam Y.K., Semple S.C., Schwank G. In vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels. Nat Biotechnol. 2021;39(8):949-957. doi 10.1038/s41587-021-00933-4Semenova A.E., Sergienko I.V., García-Giustiniani D., Monserrat L., Popova A.B., Nozadze D.N., Ezhov M.V. Verification of underlying genetic cause in a cohort of Russian patients with familial hypercholesterolemia using targeted next generation sequencing. J Cardiovasc Dev Dis. 2020;7(2):16. doi 10.3390/jcdd7020016Semenova A.E., Sergienko I.V., García-Giustiniani D., Monserrat L., Popova A.B., Nozadze D.N., Ezhov M.V. Verification of underlying genetic cause in a cohort of Russian patients with familial hypercholesterolemia using targeted next generation sequencing. J Cardiovasc Dev Dis. 2020;7(2):16. doi 10.3390/jcdd7020016Setia N., Saxena R., Arora A., Verma I.C. Spectrum of mutations in homozygous familial hypercholesterolemia in India, with four novel mutations. Atherosclerosis. 2016;255:31-36. doi 10.1016/j.atherosclerosis.2016.10.028Setia N., Saxena R., Arora A., Verma I.C. Spectrum of mutations in homozygous familial hypercholesterolemia in India, with four novel mutations. Atherosclerosis. 2016;255:31-36. doi 10.1016/j.atherosclerosis.2016.10.028Shakhtshneider E., Ivanoshchuk D., Timoshchenko O., Orlov P., Semaev S., Valeev E., Goonko A., Ladygina N., Voevoda M. Analysis of rare variants in genes related to lipid metabolism in patients with familial hypercholesterolemia in Western Siberia (Russia). J Pers Med. 2021;11(11):1232. doi 10.3390/jpm11111232Shakhtshneider E., Ivanoshchuk D., Timoshchenko O., Orlov P., Semaev S., Valeev E., Goonko A., Ladygina N., Voevoda M. Analysis of rare variants in genes related to lipid metabolism in patients with familial hypercholesterolemia in Western Siberia (Russia). J Pers Med. 2021;11(11):1232. doi 10.3390/jpm11111232Sharifi M., Walus-Miarka M., Idzior-Waluś B., Malecki M.T., Sanak M., Whittall R., Li K.W., Futema M., Humphries S.E. The genetic spectrum of familial hypercholesterolemia in south-eastern Poland. Metabolism. 2016;65(3):48-53. doi 10.1016/j.metabol.2015.10.018Sharifi M., Walus-Miarka M., Idzior-Waluś B., Malecki M.T., Sanak M., Whittall R., Li K.W., Futema M., Humphries S.E. The genetic spectrum of familial hypercholesterolemia in south-eastern Poland. Metabolism. 2016;65(3):48-53. doi 10.1016/j.metabol.2015.10.018Siegner S.M., Karasu M.E., Schröder M.S., Kontarakis Z., Corn J.E. PnB Designer: a web application to design prime and base editor guide RNAs for animals and plants. BMC Bioinformatics. 2021; 22(1):101. doi 10.1186/s12859-021-04034-6Siegner S.M., Karasu M.E., Schröder M.S., Kontarakis Z., Corn J.E. PnB Designer: a web application to design prime and base editor guide RNAs for animals and plants. BMC Bioinformatics. 2021; 22(1):101. doi 10.1186/s12859-021-04034-6Subramanian A., Sidhom E.H., Emani M., Vernon K., Sahakian N., Zhou Y., Kost-Alimova M., Slyper M., Waldman J., Dionne D., Nguyen L.T., Weins A., Marshall J.L., Rosenblatt-Rosen O., Regev A., Greka A. Single cell census of human kidney organoids shows reproducibility and diminished off-target cells after transplantation. Nat Commun. 2019;10(1):5462. doi 10.1038/S41467-019-13382-0Subramanian A., Sidhom E.H., Emani M., Vernon K., Sahakian N., Zhou Y., Kost-Alimova M., Slyper M., Waldman J., Dionne D., Nguyen L.T., Weins A., Marshall J.L., Rosenblatt-Rosen O., Regev A., Greka A. Single cell census of human kidney organoids shows reproducibility and diminished off-target cells after transplantation. Nat Commun. 2019;10(1):5462. doi 10.1038/S41467-019-13382-0Südhof T.C., Goldstein J.L., Brown M.S., Russell D.W. The LDL receptor gene: a mosaic of exons shared with different proteins. Science. 1985;228(4701):815-822. doi 10.1126/science.2988123Südhof T.C., Goldstein J.L., Brown M.S., Russell D.W. The LDL receptor gene: a mosaic of exons shared with different proteins. Science. 1985;228(4701):815-822. doi 10.1126/science.2988123Talmud P.J., Futema M., Humphries S.E. The genetic architecture of the familial hyperlipidaemia syndromes: rare mutations and common variants in multiple genes. Curr Opin Lipidol. 2014;25(4):274-281. doi 10.1097/MOL.0000000000000090Talmud P.J., Futema M., Humphries S.E. The genetic architecture of the familial hyperlipidaemia syndromes: rare mutations and common variants in multiple genes. Curr Opin Lipidol. 2014;25(4):274-281. doi 10.1097/MOL.0000000000000090Thormaehlen A.S., Schuberth C., Won H.H., Blattmann P., JoggerstThomalla B., Theiss S., Asselta R., Duga S., Merlini P.A., Ardissino D., Lander E.S., Gabriel S., Rader D.J., Peloso G.M., Pepperkok R., Kathiresan S., Runz H. Systematic cell-based phenotyping of missense alleles empowers rare variant association studies: a case for LDLR and myocardial infarction. PLoS Genet. 2015; 11(2):e1004855. doi 10.1371/journal.pgen.1004855Thormaehlen A.S., Schuberth C., Won H.H., Blattmann P., JoggerstThomalla B., Theiss S., Asselta R., Duga S., Merlini P.A., Ardissino D., Lander E.S., Gabriel S., Rader D.J., Peloso G.M., Pepperkok R., Kathiresan S., Runz H. Systematic cell-based phenotyping of missense alleles empowers rare variant association studies: a case for LDLR and myocardial infarction. PLoS Genet. 2015; 11(2):e1004855. doi 10.1371/journal.pgen.1004855Tichý L., Freiberger T., Zapletalová P., Soška V., Ravčuková B., Fajkusová L. The molecular basis of familial hypercholesterolemia in the Czech Republic: spectrum of LDLR mutations and genotypephenotype correlations. Atherosclerosis. 2012;223(2):401-408. doi 10.1016/j.atherosclerosis.2012.05.014Tichý L., Freiberger T., Zapletalová P., Soška V., Ravčuková B., Fajkusová L. The molecular basis of familial hypercholesterolemia in the Czech Republic: spectrum of LDLR mutations and genotypephenotype correlations. Atherosclerosis. 2012;223(2):401-408. doi 10.1016/j.atherosclerosis.2012.05.014Vaskova E.A., Medvedev S.P., Sorokina A.E., Nemudryy A.A., Elisaphenko E.A., Zakharova I.S., Shevchenko A.I., Kizilova E.A., ZhelezovaA.I., Evshin I.S., Sharipov R.N., Minina J.M., Zhdanova N.S., Khegay I.I., Kolpakov F.A., Sukhikh G.T., Pokushalov E.A., Karaskov A.M., Vlasov V.V., Ivanova L.N., Zakian S.M. Transcriptome characteristics and X-chromosome inactivation status in cultured rat pluripotent stem cells. Stem Cells Dev. 2015;24(24):2912-2924. doi 10.1089/scd.2015.0204Vaskova E.A., Medvedev S.P., Sorokina A.E., Nemudryy A.A., Elisaphenko E.A., Zakharova I.S., Shevchenko A.I., Kizilova E.A., ZhelezovaA.I., Evshin I.S., Sharipov R.N., Minina J.M., Zhdanova N.S., Khegay I.I., Kolpakov F.A., Sukhikh G.T., Pokushalov E.A., Karaskov A.M., Vlasov V.V., Ivanova L.N., Zakian S.M. Transcriptome characteristics and X-chromosome inactivation status in cultured rat pluripotent stem cells. Stem Cells Dev. 2015;24(24):2912-2924. doi 10.1089/scd.2015.0204Wang H., Luo Y., Li J., Guan J., Yang S., Wang Q. Generation of a gene corrected human isogenic iPSC line (CPGHi001-A-1) from a hearing loss patient with the TMC1 p.M418K mutation using CRISPR/Cas9. Stem Cell Res. 2022;60:102736. doi 10.1016/j.scr.2022.102736Wang H., Luo Y., Li J., Guan J., Yang S., Wang Q. Generation of a gene corrected human isogenic iPSC line (CPGHi001-A-1) from a hearing loss patient with the TMC1 p.M418K mutation using CRISPR/Cas9. Stem Cell Res. 2022;60:102736. doi 10.1016/j.scr.2022.102736Zakharova I.S., Shevchenko A.I., Tmoyan N.A., Elisaphenko E.A., Zubkova E.S., SleptcovA.A., Nazarenko M.S., Ezhov M.V., Kukharchuk V.V., Parfyonova Y.V., Zakian S.M. Induced pluripotent stem cell line ICGi036-A generated by reprogramming peripheral blood mononuclear cells from a patient with familial hypercholesterolemia caused due to compound heterozygous p.Ser177Leu/p.Cys352Arg mutations in LDLR. Stem Cell Res. 2022a;59:102653. doi 10.1016/j.scr.2022.102653Zakharova I.S., Shevchenko A.I., Tmoyan N.A., Elisaphenko E.A., Zubkova E.S., SleptcovA.A., Nazarenko M.S., Ezhov M.V., Kukharchuk V.V., Parfyonova Y.V., Zakian S.M. Induced pluripotent stem cell line ICGi036-A generated by reprogramming peripheral blood mononuclear cells from a patient with familial hypercholesterolemia caused due to compound heterozygous p.Ser177Leu/p.Cys352Arg mutations in LDLR. Stem Cell Res. 2022a;59:102653. doi 10.1016/j.scr.2022.102653Zakharova I.S., Shevchenko A.I., Tmoyan N.A., Elisaphenko E.A., Kalinin A.P., Sleptcov A.A., Nazarenko M.S., Ezhov M.V., Kukharchuk V.V., Parfyonova Y.V., Zakian S.M. Induced pluripotent stem cell line ICGi037-A, obtained by reprogramming peripheral blood mononuclear cells from a patient with familial hypercholesterolemia due to heterozygous p.Trp443Arg mutations in LDLR. Stem Cell Res. 2022b;60:102703. doi 10.1016/j.scr.2022.102703Zakharova I.S., Shevchenko A.I., Tmoyan N.A., Elisaphenko E.A., Kalinin A.P., Sleptcov A.A., Nazarenko M.S., Ezhov M.V., Kukharchuk V.V., Parfyonova Y.V., Zakian S.M. Induced pluripotent stem cell line ICGi037-A, obtained by reprogramming peripheral blood mononuclear cells from a patient with familial hypercholesterolemia due to heterozygous p.Trp443Arg mutations in LDLR. Stem Cell Res. 2022b;60:102703. doi 10.1016/j.scr.2022.102703Zakharova I.S., Shevchenko A.I., Tmoyan N.A., Elisaphenko E.A., Zubkova E.S., SleptcovA.A., Nazarenko M.S., Ezhov M.V., Kukharchuk V.V., Parfyonova Y.V., Zakian S.M. Induced pluripotent stem cell line ICGi038-A, obtained by reprogramming peripheral blood mononuclear cells from a patient with familial hypercholesterolemia due to compound heterozygous c.1246C>T/c.940+3_940+6del mutations in LDLR. Stem Cell Res. 2022c;60:102702. doi 10.1016/j.scr.2022.102702Zakharova I.S., Shevchenko A.I., Tmoyan N.A., Elisaphenko E.A., Zubkova E.S., SleptcovA.A., Nazarenko M.S., Ezhov M.V., Kukharchuk V.V., Parfyonova Y.V., Zakian S.M. Induced pluripotent stem cell line ICGi038-A, obtained by reprogramming peripheral blood mononuclear cells from a patient with familial hypercholesterolemia due to compound heterozygous c.1246C>T/c.940+3_940+6del mutations in LDLR. Stem Cell Res. 2022c;60:102702. doi 10.1016/j.scr.2022.102702Zakharova I.S., Shevchenko A.I., Arssan M.A., Sleptcov A.A., Nazarenko M.S., Zarubin A.A., Zheltysheva N.V., Shevchenko V.A., Tmoyan N.A., Saaya S.B., Ezhov M.V., Kukharchuk V.V., Parfyonova Y.V., Zakian S.M. IPSC-derived endothelial cells reveal LDLR dysfunction and dysregulated gene expression profiles in familial hypercholesterolemia. Int J Mol Sci. 2024a;25(2):689. doi 10.3390/ijms25020689Zakharova I.S., Shevchenko A.I., Arssan M.A., Sleptcov A.A., Nazarenko M.S., Zarubin A.A., Zheltysheva N.V., Shevchenko V.A., Tmoyan N.A., Saaya S.B., Ezhov M.V., Kukharchuk V.V., Parfyonova Y.V., Zakian S.M. IPSC-derived endothelial cells reveal LDLR dysfunction and dysregulated gene expression profiles in familial hypercholesterolemia. Int J Mol Sci. 2024a;25(2):689. doi 10.3390/ijms25020689Zakharova I.S., Shevchenko A.I., Zakian S.M. Familial hypercholesterolemia: current insight and challenges in its modelling. Pisma v Vavilovskii Zhurnal Genetiki i Selektsii = Letters to Vavilov Journal of Genetics and Breeding. 2024b;10(1):5-14. doi 10.18699/letvjgb-2024-10-2 (in Russian)Zakharova I.S., Shevchenko A.I., Zakian S.M. Familial hypercholesterolemia: current insight and challenges in its modelling. Pisma v Vavilovskii Zhurnal Genetiki i Selektsii = Letters to Vavilov Journal of Genetics and Breeding. 2024b;10(1):5-14. doi 10.18699/letvjgb-2024-10-2 (in Russian)

The authors declare that there are no conflicts of interest present.