The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, P. R. China.
Chongqing Key Laboratory of Ophthalmology, Chongqing, 400016, P. R. China.
Adv Sci (Weinh). 2023 Jun;10(16):e2206623. doi: 10.1002/advs.202206623. Epub 2023 Apr 5.
The underlying mechanisms that determine gene expression and chromatin accessibility in retinogenesis are poorly understood. Herein, single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin sequencing are performed on human embryonic eye samples obtained 9-26 weeks after conception to explore the heterogeneity of retinal progenitor cells (RPCs) and neurogenic RPCs. The differentiation trajectory from RPCs to 7 major types of retinal cells are verified. Subsequently, diverse lineage-determining transcription factors are identified and their gene regulatory networks are refined at the transcriptomic and epigenomic levels. Treatment of retinospheres, with the inhibitor of RE1 silencing transcription factor, X5050, induces more neurogenesis with the regular arrangement, and a decrease in Müller glial cells. The signatures of major retinal cells and their correlation with pathogenic genes associated with multiple ocular diseases, including uveitis and age-related macular degeneration are also described. A framework for the integrated exploration of single-cell developmental dynamics of the human primary retina is provided.
视网膜发生过程中决定基因表达和染色质可及性的潜在机制还不太清楚。在此，对人胚胎眼样本进行单细胞 RNA 测序和转座酶可及染色质测序单细胞分析，以探索视网膜祖细胞 (RPCs) 和神经发生性 RPCs 的异质性。验证了从 RPCs 到 7 种主要视网膜细胞的分化轨迹。随后，鉴定出多种谱系决定转录因子，并在转录组和表观基因组水平上对其基因调控网络进行了精细化研究。用 RE1 沉默转录因子抑制剂 X5050 处理视网膜球体，可诱导更多具有正常排列的神经发生，并减少 Müller 胶质细胞。还描述了主要视网膜细胞的特征及其与与多种眼部疾病（包括葡萄膜炎和年龄相关性黄斑变性）相关的致病基因的相关性。为整合探索人原发性视网膜的单细胞发育动力学提供了一个框架。
