A Novel Isogenic Human Cell-Based System for MEN1 Syndrome Generated by CRISPR/Cas9 Genome Editing

Multiple endocrine neoplasia type 1 (MEN1) is a rare tumor syndrome that manifests differently among various patients. Despite the mutations in the <i>MEN1</i> gene that commonly predispose tumor development, there are no obvious phenotype–genotype correlations. The existing animal and i...

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Autores principales:	Natalia Klementieva, Daria Goliusova, Julia Krupinova, Vladislav Yanvarev, Alexandra Panova, Natalia Mokrysheva, Sergey L. Kiselev
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	MEN1 induced pluripotent stem cells CRISPR/Cas9 genome editing isogenic cell lines definitive endoderm differentiation Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/a116548ab2ac42498babf5e1ff263192
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spelling	oai:doaj.org-article:a116548ab2ac42498babf5e1ff2631922021-11-11T17:27:07ZA Novel Isogenic Human Cell-Based System for MEN1 Syndrome Generated by CRISPR/Cas9 Genome Editing10.3390/ijms2221120541422-00671661-6596https://doaj.org/article/a116548ab2ac42498babf5e1ff2631922021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/12054https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Multiple endocrine neoplasia type 1 (MEN1) is a rare tumor syndrome that manifests differently among various patients. Despite the mutations in the <i>MEN1</i> gene that commonly predispose tumor development, there are no obvious phenotype–genotype correlations. The existing animal and in vitro models do not allow for studies of the molecular genetics of the disease in a human-specific context. We aimed to create a new human cell-based model, which would consider the variability in genetic or environmental factors that cause the complexity of MEN1 syndrome. Here, we generated patient-specific induced pluripotent stem cell lines carrying the mutation c.1252G>T, D418Y in the <i>MEN1</i> gene. To reduce the genetically determined variability of the existing cellular models, we created an isogenic cell system by modifying the target allele through CRISPR/Cas9 editing with great specificity and efficiency. The high potential of these cell lines to differentiate into the endodermal lineage in defined conditions ensures the next steps in the development of more specialized cells that are commonly affected in MEN1 patients, such as parathyroid or pancreatic islet cells. We anticipate that this isogenic system will be broadly useful to comprehensively study <i>MEN1</i> gene function across different contexts, including in vitro modeling of MEN1 syndrome.Natalia KlementievaDaria GoliusovaJulia KrupinovaVladislav YanvarevAlexandra PanovaNatalia MokryshevaSergey L. KiselevMDPI AGarticleMEN1induced pluripotent stem cellsCRISPR/Cas9 genome editingisogenic cell linesdefinitive endoderm differentiationBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12054, p 12054 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	MEN1 induced pluripotent stem cells CRISPR/Cas9 genome editing isogenic cell lines definitive endoderm differentiation Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	MEN1 induced pluripotent stem cells CRISPR/Cas9 genome editing isogenic cell lines definitive endoderm differentiation Biology (General) QH301-705.5 Chemistry QD1-999 Natalia Klementieva Daria Goliusova Julia Krupinova Vladislav Yanvarev Alexandra Panova Natalia Mokrysheva Sergey L. Kiselev A Novel Isogenic Human Cell-Based System for MEN1 Syndrome Generated by CRISPR/Cas9 Genome Editing
description	Multiple endocrine neoplasia type 1 (MEN1) is a rare tumor syndrome that manifests differently among various patients. Despite the mutations in the <i>MEN1</i> gene that commonly predispose tumor development, there are no obvious phenotype–genotype correlations. The existing animal and in vitro models do not allow for studies of the molecular genetics of the disease in a human-specific context. We aimed to create a new human cell-based model, which would consider the variability in genetic or environmental factors that cause the complexity of MEN1 syndrome. Here, we generated patient-specific induced pluripotent stem cell lines carrying the mutation c.1252G>T, D418Y in the <i>MEN1</i> gene. To reduce the genetically determined variability of the existing cellular models, we created an isogenic cell system by modifying the target allele through CRISPR/Cas9 editing with great specificity and efficiency. The high potential of these cell lines to differentiate into the endodermal lineage in defined conditions ensures the next steps in the development of more specialized cells that are commonly affected in MEN1 patients, such as parathyroid or pancreatic islet cells. We anticipate that this isogenic system will be broadly useful to comprehensively study <i>MEN1</i> gene function across different contexts, including in vitro modeling of MEN1 syndrome.
format	article
author	Natalia Klementieva Daria Goliusova Julia Krupinova Vladislav Yanvarev Alexandra Panova Natalia Mokrysheva Sergey L. Kiselev
author_facet	Natalia Klementieva Daria Goliusova Julia Krupinova Vladislav Yanvarev Alexandra Panova Natalia Mokrysheva Sergey L. Kiselev
author_sort	Natalia Klementieva
title	A Novel Isogenic Human Cell-Based System for MEN1 Syndrome Generated by CRISPR/Cas9 Genome Editing
title_short	A Novel Isogenic Human Cell-Based System for MEN1 Syndrome Generated by CRISPR/Cas9 Genome Editing
title_full	A Novel Isogenic Human Cell-Based System for MEN1 Syndrome Generated by CRISPR/Cas9 Genome Editing
title_fullStr	A Novel Isogenic Human Cell-Based System for MEN1 Syndrome Generated by CRISPR/Cas9 Genome Editing
title_full_unstemmed	A Novel Isogenic Human Cell-Based System for MEN1 Syndrome Generated by CRISPR/Cas9 Genome Editing
title_sort	novel isogenic human cell-based system for men1 syndrome generated by crispr/cas9 genome editing
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a116548ab2ac42498babf5e1ff263192
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A Novel Isogenic Human Cell-Based System for MEN1 Syndrome Generated by CRISPR/Cas9 Genome Editing

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