生成用于模拟与不确定潜能克隆性造血相关心血管疾病的纯合DNMT3A基因敲除人诱导多能干细胞系。
Generation of a homozygous DNMT3A knock-out hiPSC line for modeling of cardiovascular diseases associated with clonal hematopoiesis of indeterminate potential.
作者信息
Triantafyllou Christos, Peitz Michael, Fleischmann Bernd K, Rieck Sarah
机构信息
Institute of Physiology I, University of Bonn, Medical Faculty, Bonn, Germany.
Cell Programming Core Facility, University of Bonn, Medical Faculty, Bonn, Germany.
出版信息
Stem Cell Res. 2025 Aug;86:103707. doi: 10.1016/j.scr.2025.103707. Epub 2025 Apr 5.
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.
与不确定潜能的克隆性造血（CHIP）相关的突变已与心血管疾病（CVD）相关联，其中DNA甲基转移酶3A（DNMT3A）是最常发生突变的基因。（贾斯瓦尔等人，2017年；阿布普拉纳尔普等人，2021年）我们生成了一个经基因组编辑的人类诱导多能干细胞（hiPSC）系，该细胞系中DNMT3A基因纯合敲除（KO），以模拟功能丧失突变，同时还生成了一个等基因模拟处理对照系（模拟对照）。为了进行质量控制，我们测试了这些hiPSC系的多能性及其分化为三个胚层的能力。这些细胞系的产生有助于分析与DNMT3A相关的、CHIP相关的心血管疾病的细胞病理机制。
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