Generation of a homozygous DNMT3A knock-out hiPSC line for modeling of cardiovascular diseases associated with clonal hematopoiesis of indeterminate potential

Mutations associated with clonal hematopoiesis of indeterminate potential (CHIP) have been linked to cardiovascular disease (CVD), with DNA methyltransferase 3A (DNMT3A) being the most commonly mutated gene. (Jaiswal et al. 2017; Abplanalp et al. 2021) We generated a genome-edited human induced plur...

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Main Authors: Christos Triantafyllou, Michael Peitz, Bernd K. Fleischmann, Sarah Rieck
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Stem Cell Research
Online Access:http://www.sciencedirect.com/science/article/pii/S1873506125000571
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author Christos Triantafyllou
Michael Peitz
Bernd K. Fleischmann
Sarah Rieck
author_facet Christos Triantafyllou
Michael Peitz
Bernd K. Fleischmann
Sarah Rieck
author_sort Christos Triantafyllou
collection DOAJ
description Mutations associated with clonal hematopoiesis of indeterminate potential (CHIP) have been linked to cardiovascular disease (CVD), with DNA methyltransferase 3A (DNMT3A) being the most commonly mutated gene. (Jaiswal et al. 2017; Abplanalp et al. 2021) We generated a genome-edited human induced pluripotent stem cell (hiPSC) line with a homozygous knock-out (KO) of DNMT3A, to mimic loss-of-function mutations, and an isogenic mock-treated control line (mock ctrl). For quality control, we tested the pluripotency of these hiPSC lines and their ability to differentiate into the three germ layers. The generation of these cell lines enables the analysis of cellular pathomechanisms of DNMT3A-related, CHIP-associated CVDs.
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spelling doaj-art-b666fd051e614d81a53cd05d0ed4d4fe2025-08-20T02:33:12ZengElsevierStem Cell Research1873-50612025-08-018610370710.1016/j.scr.2025.103707Generation of a homozygous DNMT3A knock-out hiPSC line for modeling of cardiovascular diseases associated with clonal hematopoiesis of indeterminate potentialChristos Triantafyllou0Michael Peitz1Bernd K. Fleischmann2Sarah Rieck3Institute of Physiology I, University of Bonn, Medical Faculty, Bonn, GermanyCell Programming Core Facility, University of Bonn, Medical Faculty, Bonn, GermanyInstitute of Physiology I, University of Bonn, Medical Faculty, Bonn, GermanyInstitute of Physiology I, University of Bonn, Medical Faculty, Bonn, Germany; Corresponding author.Mutations associated with clonal hematopoiesis of indeterminate potential (CHIP) have been linked to cardiovascular disease (CVD), with DNA methyltransferase 3A (DNMT3A) being the most commonly mutated gene. (Jaiswal et al. 2017; Abplanalp et al. 2021) We generated a genome-edited human induced pluripotent stem cell (hiPSC) line with a homozygous knock-out (KO) of DNMT3A, to mimic loss-of-function mutations, and an isogenic mock-treated control line (mock ctrl). For quality control, we tested the pluripotency of these hiPSC lines and their ability to differentiate into the three germ layers. The generation of these cell lines enables the analysis of cellular pathomechanisms of DNMT3A-related, CHIP-associated CVDs.http://www.sciencedirect.com/science/article/pii/S1873506125000571
spellingShingle Christos Triantafyllou
Michael Peitz
Bernd K. Fleischmann
Sarah Rieck
Generation of a homozygous DNMT3A knock-out hiPSC line for modeling of cardiovascular diseases associated with clonal hematopoiesis of indeterminate potential
Stem Cell Research
title Generation of a homozygous DNMT3A knock-out hiPSC line for modeling of cardiovascular diseases associated with clonal hematopoiesis of indeterminate potential
title_full Generation of a homozygous DNMT3A knock-out hiPSC line for modeling of cardiovascular diseases associated with clonal hematopoiesis of indeterminate potential
title_fullStr Generation of a homozygous DNMT3A knock-out hiPSC line for modeling of cardiovascular diseases associated with clonal hematopoiesis of indeterminate potential
title_full_unstemmed Generation of a homozygous DNMT3A knock-out hiPSC line for modeling of cardiovascular diseases associated with clonal hematopoiesis of indeterminate potential
title_short Generation of a homozygous DNMT3A knock-out hiPSC line for modeling of cardiovascular diseases associated with clonal hematopoiesis of indeterminate potential
title_sort generation of a homozygous dnmt3a knock out hipsc line for modeling of cardiovascular diseases associated with clonal hematopoiesis of indeterminate potential
url http://www.sciencedirect.com/science/article/pii/S1873506125000571
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