PDF(Pubmed)
Abstract：
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.
摘要：
对视网膜发生中决定基因表达和染色质可及性的潜在机制知之甚少。在这里，对受孕后9-26周获得的人胚胎眼样本进行单细胞RNA测序和转座酶可接近染色质测序的单细胞测定,以探索视网膜祖细胞(RPCs)和神经源性RPCs的异质性.验证了从RPC到7种主要类型视网膜细胞的分化轨迹。随后，鉴定了多种谱系决定转录因子，并在转录组和表观基因组水平上完善了它们的基因调控网络。治疗视网膜球体，与RE1沉默转录因子的抑制剂，X5050，诱导更多的神经发生与规则的排列，Müller胶质细胞减少.主要视网膜细胞的特征及其与多种眼部疾病相关的致病基因的相关性，还描述了包括葡萄膜炎和年龄相关性黄斑变性。提供了用于人类原代视网膜的单细胞发育动力学的综合探索的框架。
