Molecular Classification and Comparative Taxonomics of Foveal and Peripheral Cells in Primate Retina
Molecular Classification and Comparative Taxonomics of Foveal and Peripheral Cells in Primate Retina
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DOI：
10.1016/j.cell.2019.01.004
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发表时间：
2019-02-21
期刊：
影响因子：
64.5
通讯作者：
Sanes, Joshua R.
中科院分区：
文献类型：
--
作者：
Peng, Yi-Rong;Shekhar, Karthik;Sanes, Joshua R.
灵长类动物（包括人类）的高敏锐度视力是由称为中央凹的视网膜中央区域调节的。由于更容易接近的生物体缺乏中央凹，因此人们对它的特殊功能及其在眼部疾病中的功能障碍仍然知之甚少。我们使用 165,000 个单细胞 RNA 测序图谱来生成猕猴中央凹和周边视网膜的全面细胞分类。超过 60 种细胞类型中超过 80% 在两个区域之间匹配，但在比例和基因表达方面表现出显着差异，其中一些与功能差异有关。猕猴视网膜类型与小鼠视网膜类型的比较表明，中间神经元类型是严格保守的。相比之下，尽管表现出保守的转录因子代码，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，可以绘制与 7 种人类视网膜疾病相关的 >190 个基因的细胞类型和区域特异性表达图谱。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。
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.