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眼后段的转录组分析完成了人类眼睛的细胞图谱。

Transcriptomic Analysis of the Ocular Posterior Segment Completes a Cell Atlas of the Human Eye.

作者信息

Monavarfeshani Aboozar, Yan Wenjun, Pappas Christian, Odenigbo Kenechukwu A, He Zhigang, Segrè Ayellet V, van Zyl Tavé, Hageman Gregory S, Sanes Joshua R

机构信息

Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138.

F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA.

出版信息

bioRxiv. 2023 Apr 27:2023.04.26.538447. doi: 10.1101/2023.04.26.538447.

Abstract

Although the visual system extends through the brain, most vision loss originates from defects in the eye. Its central element is the neural retina, which senses light, processes visual signals, and transmits them to the rest of the brain through the optic nerve (ON). Surrounding the retina are numerous other structures, conventionally divided into anterior and posterior segments. Here we used high-throughput single nucleus RNA sequencing (snRNA-seq) to classify and characterize cells in the extraretinal components of the posterior segment: ON, optic nerve head (ONH), peripheral sclera, peripapillary sclera (PPS), choroid, and retinal pigment epithelium (RPE). Defects in each of these tissues are associated with blinding diseases - for example, glaucoma (ONH and PPS), optic neuritis (ON), retinitis pigmentosa (RPE), and age-related macular degeneration (RPE and choroid). From ∼151,000 single nuclei, we identified 37 transcriptomically distinct cell types, including multiple types of astrocytes, oligodendrocytes, fibroblasts, and vascular endothelial cells. Our analyses revealed a differential distribution of many cell types among distinct structures. Together with our previous analyses of the anterior segment and retina, the new data complete a "Version 1" cell atlas of the human eye. We used this atlas to map the expression of >180 genes associated with the risk of developing glaucoma, which is known to involve ocular tissues in both anterior and posterior segments as well as neural retina. Similar methods can be used to investigate numerous additional ocular diseases, many of which are currently untreatable.

摘要

尽管视觉系统贯穿大脑,但大多数视力丧失源于眼睛的缺陷。其核心要素是神经视网膜,它能感知光线、处理视觉信号,并通过视神经将信号传递到大脑的其他部分。视网膜周围还有许多其他结构,传统上分为前段和后段。在这里,我们使用高通量单核RNA测序(snRNA-seq)对后段视网膜外成分中的细胞进行分类和表征:视神经、视神经乳头(视盘)、周边巩膜、视乳头周围巩膜(PPS)、脉络膜和视网膜色素上皮(RPE)。这些组织中的每一个出现缺陷都与致盲疾病相关——例如,青光眼(视盘和PPS)、视神经炎(视神经)、色素性视网膜炎(RPE)和年龄相关性黄斑变性(RPE和脉络膜)。从约151,000个单核中,我们鉴定出37种转录组不同的细胞类型,包括多种星形胶质细胞、少突胶质细胞、成纤维细胞和血管内皮细胞。我们的分析揭示了许多细胞类型在不同结构中的差异分布。连同我们之前对前段和视网膜的分析,这些新数据完善了人类眼睛的“版本1”细胞图谱。我们使用这个图谱来绘制与青光眼发病风险相关的180多个基因的表达图谱,已知青光眼涉及前段和后段的眼组织以及神经视网膜。类似的方法可用于研究许多其他眼部疾病,其中许多目前无法治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d96f/10168356/c55c161216e3/nihpp-2023.04.26.538447v1-f0001.jpg

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