Beijing Advanced Innovation Center for Genomics, Department of Obstetrics and Gynecology, Third Hospital, College of Life Sciences, Peking University, Beijing, China.
Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Biomedical Pioneering Innovation Center, Peking University, Beijing, China.
PLoS Biol. 2019 Jul 3;17(7):e3000365. doi: 10.1371/journal.pbio.3000365. eCollection 2019 Jul.
The developmental pathway of the neural retina (NR) and retinal pigment epithelium (RPE) has been revealed by extensive research in mice. However, the molecular mechanisms underlying the development of the human NR and RPE, as well as the interactions between these two tissues, have not been well defined. Here, we analyzed 2,421 individual cells from human fetal NR and RPE using single-cell RNA sequencing (RNA-seq) technique and revealed the tightly regulated spatiotemporal gene expression network of human retinal cells. We identified major cell classes of human fetal retina and potential crucial transcription factors for each cell class. We dissected the dynamic expression patterns of visual cycle- and ligand-receptor interaction-related genes in the RPE and NR. Moreover, we provided a map of disease-related genes for human fetal retinal cells and highlighted the importance of retinal progenitor cells as potential targets of inherited retinal diseases. Our findings captured the key in vivo features of the development of the human NR and RPE and offered insightful clues for further functional studies.
神经视网膜（NR）和视网膜色素上皮（RPE）的发育途径已经通过对小鼠的广泛研究揭示出来。然而，人类 NR 和 RPE 发育的分子机制以及这两种组织之间的相互作用尚未得到很好的定义。在这里，我们使用单细胞 RNA 测序（RNA-seq）技术分析了来自人类胎儿 NR 和 RPE 的 2421 个单个细胞，并揭示了人类视网膜细胞的严格调控的时空基因表达网络。我们鉴定了人类胎儿视网膜的主要细胞类型和每个细胞类型的潜在关键转录因子。我们剖析了 RPE 和 NR 中与视觉循环和配体-受体相互作用相关基因的动态表达模式。此外，我们为人类胎儿视网膜细胞提供了疾病相关基因图谱，并强调了视网膜祖细胞作为遗传性视网膜疾病潜在靶点的重要性。我们的研究结果捕捉到了人类 NR 和 RPE 发育的关键体内特征，并为进一步的功能研究提供了有见地的线索。
