Human Pluripotent Stem Cell-derived Adrenocortical Cells Model KCNJ5 Mutation in Primary Aldosteronism

Our study aimed to create a more effective model for researching adrenocortical diseases by improving the differentiation process of human induced pluripotent stem cells (hiPSCs) into adrenocortical cells. We wanted a system that mimics natural hormone production and allows for easy genetic manipulation. By expressing a key factor, steroidogenic factor-1 (SF-1), and adding essential niche factors, we successfully generated cells that produce adrenal steroids like aldosterone. These cells showed gene expression patterns similar to those of fetal and adult adrenal cortex cells, responded to natural stimuli, and kept their ability to proliferate. By using CRISPR/Cas9 to introduce a KCNJ5 mutation associated with primary aldosteronism, we observed increased aldosterone production and cell growth, which are crucial for studying tumor development. This new system offers a valuable tool for better understanding adrenocortical diseases and developing new treatments.Here, we provide our annotated single-cell RNA sequencing data as a Seurat object (Seurat v5.0.1).本研究旨在通过优化人类诱导多能干细胞（human induced pluripotent stem cells, hiPSCs）向肾上腺皮质细胞的分化流程，构建用于肾上腺皮质疾病研究的高效模型。我们期望构建一套能够模拟天然激素生成过程、且便于开展基因操作的研究体系。通过过表达关键转录因子类固醇生成因子-1（steroidogenic factor-1, SF-1）并添加核心微环境因子，我们成功获得了可分泌醛固酮等肾上腺类固醇激素的细胞。该细胞的基因表达谱与胎儿及成人肾上腺皮质细胞高度相似，可对天然生理刺激产生特异性应答，且维持了正常的增殖能力。利用CRISPR/Cas9技术引入与原发性醛固酮增多症相关的KCNJ5突变后，我们观测到醛固酮分泌量与细胞增殖活性均显著升高，这一表型对肾上腺皮质肿瘤发生发展的研究具有关键意义。这套全新的研究体系为深入解析肾上腺皮质疾病的发病机制及开发新型治疗策略提供了极具价值的研究工具。本研究附带提供经过注释的单细胞RNA测序数据，其存储格式为Seurat对象（Seurat v5.0.1）。