通过CRISPR对POMC:W84X突变进行校正，生成等基因iPSC系，用于单基因肥胖建模。

IF 0.7 4区医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Stem cell research Pub Date : 2025-07-25 DOI:10.1016/j.scr.2025.103786

Katarzyna A. Ludwik , Valeria Fernandez Valone , Regina Jahn , Sabine Jyrch , Lara Lechner , Peter Kühnen , Harald Stachelscheid

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引用次数: 0

摘要

我们报道了一种遗传校正诱导多能干细胞（iPSC）系BIHi261-A-1的产生，该系来源于患者特异性iPSC系BIHi261-A，该系携带POMC基因（POMC:W84X）的纯合截断突变。这种突变通过破坏促黑色素皮质素的功能导致单基因肥胖。使用CRISPR-Cas9编辑对致病变异进行校正。由此产生的iPSC系保持了正常的核型，表达了多能性标记，并保留了向所有三个胚层分化的能力。BIHi261-A-1为pomc相关肥胖和下丘脑能量稳态调节的疾病建模和治疗研究提供了有价值的等基因控制。

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Generation of an isogenic iPSC line via CRISPR correction of the POMC:W84X mutation for monogenic obesity modeling

We report the generation of a genetically corrected induced pluripotent stem cell (iPSC) line, BIHi261-A-1, derived from the patient-specific iPSC line BIHi261-A carrying a homozygous truncating mutation in the POMC gene (POMC:W84X). This mutation causes monogenic obesity by disrupting proopiomelanocortin function. The pathogenic variant was corrected using CRISPR-Cas9 editing. The resulting iPSC line maintained a normal karyotype, expressed pluripotency markers, and retained the ability to differentiate into all three germ layers. BIHi261-A-1 provides valuable isogenic control for disease modeling and therapeutic research targeting POMC-related obesity and hypothalamic regulation of energy homeostasis.

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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.