Table3_A Single-Cell Transcriptome Atlas of the Human Retinal Pigment Epithelium.xlsx

Human retinal pigment epithelium cells are arranged in a monolayer that plays an important supporting role in the retina. Although the heterogeneity of specific retinal cells has been well studied, the diversity of hRPE cells has not been reported. Here, we performed a single-cell RNA sequencing on 9,302 hRPE cells from three donors and profiled a transcriptome atlas. Our results identified two subpopulations that exhibit substantial differences in gene expression patterns and functions. One of the clusters specifically expressed ID3, a macular retinal pigment epithelium marker. The other cluster highly expressed CRYAB, a peripheral RPE marker. Our results also showed that the genes associated with oxidative stress and endoplasmic reticulum stress were more enriched in the macular RPE. The genes related to light perception, oxidative stress and lipid metabolism were more enriched in the peripheral RPE. Additionally, we provided a map of disease-related genes in the hRPE and highlighted the importance of the macular RPE and peripheral RPE clusters P4 and P6 as potential therapeutic targets for retinal diseases. Our study provides a transcriptional landscape for the human retinal pigment epithelium that is critical to understanding retinal biology and disease.

人视网膜色素上皮细胞（human retinal pigment epithelium, RPE）以单层形式排布，在视网膜中发挥关键支持功能。尽管学界已对特定视网膜细胞的异质性开展了充分研究，但人RPE细胞的多样性尚未见诸报道。本研究对3名供体来源的9302个人RPE细胞进行了单细胞RNA测序，构建了其转录组图谱。研究结果鉴定出两个细胞亚群，二者在基因表达模式与功能层面均存在显著差异。其中一个细胞簇特异性表达ID3，该分子为黄斑区RPE的标记物；另一细胞簇高表达CRYAB，为外周区RPE的标记物。研究同时发现，与氧化应激及内质网应激相关的基因在黄斑区RPE中富集程度更高，而与光感知、氧化应激及脂质代谢相关的基因则在外周区RPE中富集更为显著。此外，本研究绘制了人RPE细胞的疾病相关基因图谱，并强调黄斑区RPE与外周区RPE的P4、P6细胞簇可作为视网膜疾病潜在治疗靶点的重要价值。本研究为人类RPE细胞构建了转录组全景图谱，这对解析视网膜生物学特性及疾病机制具有关键意义。