A single-cell transcriptome atlas of the adult human retina
A single-cell transcriptome atlas of the adult human retina
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DOI：
10.15252/embj.2018100811
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发表时间：
2019-09-16
期刊：
影响因子：
11.4
通讯作者：
Wong, Raymond C. B.
中科院分区：
文献类型：
--
作者：
Lukowski, Samuel W.;Lo, Camden Y.;Wong, Raymond C. B.
视网膜是一种专门的神经组织，它能感知光线并启动图像处理。虽然特定视网膜细胞的功能组织已经得到了很好的研究，但人类许多细胞类型的分子特征仍然不清楚。为了全面分析人类视网膜，我们对来自三个供体的20，009个细胞进行了单细胞RNA测序，并编制了参考转录组图谱。使用无监督聚类分析，我们鉴定了18个转录不同的细胞群，代表所有已知的神经视网膜细胞：视杆光感受器、视锥光感受器、Muller胶质细胞、双极细胞、无长突细胞、视网膜神经节细胞、水平细胞、星形胶质细胞和小胶质细胞。我们的数据捕获了健康和推定的早期退化视杆细胞的分子特征，并揭示了MALAT1表达的丧失与较长的死后时间，这可能表明MALAT1在视杆细胞变性中的新作用。我们已经证明了使用这个视网膜转录组图谱基准多能干细胞衍生的视锥光感受器和成人Muller神经胶质细胞系。这项工作为人类视网膜细胞的转录景观提供了前所未有的见解，这是理解视网膜生物学和疾病的基础。
The retina is a specialized neural tissue that senses light and initiates image processing. Although the functional organization of specific retina cells has been well studied, the molecular profile of many cell types remains unclear in humans. To comprehensively profile the human retina, we performed single-cell RNA sequencing on 20,009 cells from three donors and compiled a reference transcriptome atlas. Using unsupervised clustering analysis, we identified 18 transcriptionally distinct cell populations representing all known neural retinal cells: rod photoreceptors, cone photoreceptors, Muller glia, bipolar cells, amacrine cells, retinal ganglion cells, horizontal cells, astrocytes, and microglia. Our data captured molecular profiles for healthy and putative early degenerating rod photoreceptors, and revealed the loss of MALAT1 expression with longer post-mortem time, which potentially suggested a novel role of MALAT1 in rod photoreceptor degeneration. We have demonstrated the use of this retina transcriptome atlas to benchmark pluripotent stem cell-derived cone photoreceptors and an adult Muller glia cell line. This work provides an important reference with unprecedented insights into the transcriptional landscape of human retinal cells, which is fundamental to understanding retinal biology and disease.