来自ACVRL1 c.1042delG突变的遗传性出血性毛细血管扩张2型患者的患者源性和基因校正的hiPSC系的产生

IF 0.7 4区医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Stem cell research Pub Date : 2025-08-21 DOI:10.1016/j.scr.2025.103812

Kendy E. Urdaneta , Francijna E. van den Hil , Marga J. Bouma , Herak Manjikian , Christine L. Mummery , Christian M.A.H. Freund , Valeria V. Orlova , Sebastiaan J. van Kampen

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引用次数: 0

摘要

遗传性出血性毛细血管扩张2型（HHT2）是一种由ACVRL1突变引起的血管疾病。我们通过重编程皮肤成纤维细胞，从两名ACVRL1 （c.1042delG）外显子7杂合缺失1 bp的ht2患者身上获得了人诱导多能干细胞（hiPSC）系。使用CRISPR-Cas9构建基因校正的等基因hiPSCs。所有细胞系核型正常，表达未分化状态标记，体外分化为所有胚层，无脱靶效应。这些来自患者的遗传匹配的hiPSC对为ht2体外建模和研究发病机制提供了一个强大的平台。

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Generation of patient-derived and gene-corrected hiPSC lines from Hereditary Hemorrhagic Telangiectasia type 2 patients with ACVRL1 c.1042delG mutation

Hereditary Hemorrhagic Telangiectasia type 2 (HHT2) is a vascular disorder caused by mutations in ACVRL1. We generated human induced pluripotent stem cell (hiPSC) lines from two HHT2 patients with a heterozygous 1 bp deletion in exon 7 of ACVRL1 (c.1042delG) by reprogramming skin fibroblasts. Gene-corrected isogenic hiPSCs were created using CRISPR-Cas9. All lines displayed normal karyotypes, expressed markers of the undifferentiated state, differentiated into all germ layers in vitro, and showed no off-target effects. These patient-derived, genetically matched hiPSC pairs provide a robust platform for modeling HHT2 in vitro and investigating molecular mechanisms of pathogenesis.

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来源期刊

Stem cell research 生物-生物工程与应用微生物

CiteScore

2.20

自引率

8.30%

发文量

338

审稿时长

55 days

期刊介绍： Stem Cell Research is dedicated to publishing high-quality manuscripts focusing on the biology and applications of stem cell research. Submissions to Stem Cell Research, may cover all aspects of stem cells, including embryonic stem cells, tissue-specific stem cells, cancer stem cells, developmental studies, stem cell genomes, and translational research. Stem Cell Research publishes 6 issues a year.