Zhao Yingke, Cheng Yun, Li Ting, Wu Jiawen, Li Chenchen, Zhang Shenghai, Wu Jihong
Department of Ophthalmology, Eye and ENT Hospital, College of Medicine, Fudan University, Shanghai, 200000, China.
Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality, Shanghai, 200000, China.
Sci Data. 2025 May 27;12(1):878. doi: 10.1038/s41597-025-05079-5.
Stargardt disease (STGD), predominantly caused by mutations in the ABCA4 gene, is a leading cause of inherited retinal degeneration. Although several lines of mice expressing disease-causing variants have been produced, mice due to the lack of macular may not be the perfect model to mimic the characteristics of STGD. To address this knowledge gap, we generated retinal organoids from patient-derived induced pluripotent stem cells (iPSCs) harboring ABCA4 mutations and performed biological validation. The generated retinal organoids were subjected to single-cell RNA sequencing (scRNA-seq) at major developmental stages (40, 90, 150, 200, and 260 days), and we additionally compared the transcriptomics with our recently published control retinal organoids to further confirm the reliability of the dataset. By using iPSCs carrying most common variant in Chinese STGD patients, the dataset not only provides a powerful resource for studying STGD, but also offers novels insight into the developmental mechanisms underlying ABCA4-associated pathological changes in the retinal organoid system.
斯塔加特病（STGD）主要由ABCA4基因突变引起，是遗传性视网膜变性的主要原因。尽管已经培育出了几种表达致病变体的小鼠品系，但由于缺乏黄斑，这些小鼠可能不是模拟STGD特征的完美模型。为了填补这一知识空白，我们从携带ABCA4突变的患者来源的诱导多能干细胞（iPSC）中生成了视网膜类器官，并进行了生物学验证。在主要发育阶段（40、90、150、200和260天）对生成的视网膜类器官进行单细胞RNA测序（scRNA-seq），此外，我们还将转录组学与我们最近发表的对照视网膜类器官进行了比较，以进一步确认数据集的可靠性。通过使用携带中国STGD患者中最常见变体的iPSC，该数据集不仅为研究STGD提供了强大的资源，还为视网膜类器官系统中ABCA4相关病理变化的发育机制提供了新的见解。
