Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Cell. 2019 Feb 21;176(5):1222-1237.e22. doi: 10.1016/j.cell.2019.01.004. Epub 2019 Jan 31.
High-acuity vision in primates, including humans, is mediated by a small central retinal region called the fovea. As more accessible organisms lack a fovea, its specialized function and its dysfunction in ocular diseases remain poorly understood. We used 165,000 single-cell RNA-seq profiles to generate comprehensive cellular taxonomies of macaque fovea and peripheral retina. More than 80% of >60 cell types match between the two regions but exhibit substantial differences in proportions and gene expression, some of which we relate to functional differences. Comparison of macaque retinal types with those of mice reveals that interneuron types are tightly conserved. In contrast, projection neuron types and programs diverge, despite exhibiting conserved transcription factor codes. Key macaque types are conserved in humans, allowing mapping of cell-type and region-specific expression of >190 genes associated with 7 human retinal diseases. Our work provides a framework for comparative single-cell analysis across tissue regions and species.
灵长类动物(包括人类)的高敏锐度视觉是由一个称为中央凹的小视网膜区域介导的。由于更易接近的生物体缺乏中央凹,因此其特殊功能及其在眼部疾病中的功能障碍仍知之甚少。我们使用了 165,000 个单细胞 RNA-seq 图谱,生成了猕猴中央凹和周边视网膜的全面细胞分类群。超过 60 种细胞类型中的 80%以上在这两个区域之间匹配,但在比例和基因表达方面存在很大差异,其中一些我们与功能差异有关。将猕猴的视网膜类型与小鼠进行比较表明,中间神经元类型是紧密保守的。相比之下,尽管转录因子代码保守,但投射神经元类型和程序却有所不同。关键的猕猴类型在人类中是保守的,这使得与 7 种人类视网膜疾病相关的超过 190 个基因的细胞类型和区域特异性表达图谱得以绘制。我们的工作为跨组织区域和物种的比较单细胞分析提供了框架。