GENE EXPRESSION WITHIN A HUMAN CHOROIDAL NEOVASCULAR MEMBRANE USING SPATIAL TRANSCRIPTOMICS.
GENE EXPRESSION WITHIN A HUMAN CHOROIDAL NEOVASCULAR MEMBRANE USING SPATIAL TRANSCRIPTOMICS.
复制标题
使用空间转录组学在人类脉络膜新生血管膜内进行基因表达。
DOI：
10.1101/2023.06.16.544770
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Mullins,RobertF
中科院分区：
文献类型：
--
作者：
Voigt,AndrewP;Mullin,NathanielK;Navratil,EmmaM;Flamme-Wiese,MilesJ;Lin,Li-Chun;Scheetz,ToddE;Han,IanC;Stone,EdwinM;Tucker,BuddA;Mullins,RobertF
目的：黄斑新生血管是年龄相关性黄斑变性的一种相对常见的并发症，具有潜在的视觉破坏性。在黄斑新生血管，病理性血管生成可以起源于脉络膜或视网膜，但我们有有限的了解如何不同的细胞类型变得失调，在这个动态的process.Methods：要研究基因表达是如何改变的病理焦点领域，我们进行了空间RNA测序的人供体眼睛与黄斑新生血管以及健康对照供体。我们进行了差异表达，以确定丰富的基因在该地区的黄斑新生血管和使用去卷积算法来预测这些失调的基因的起源细胞类型。结果：在该地区的新生血管，内皮细胞表现出增加的基因表达的Rho家族GT3信号和整合素信号。同样，VEGF和TGFB1被确定为潜在的上游调节因子，可以驱动黄斑新生血管供体中内皮细胞和视网膜色素上皮细胞产生的观察到的基因表达变化。将这些空间基因表达谱与先前在人类年龄相关性黄斑变性中的单细胞基因表达实验以及小鼠中激光诱导的新血管形成模型进行比较。作为第二个目标，我们调查了区域内的黄斑神经视网膜和黄斑和周边choroid.Conclusions之间的基因表达模式：总体而言，这项研究在空间上分析了整个视网膜，视网膜色素上皮细胞和脉络膜在健康的基因表达，并描述了一组候选分子，成为失调的黄斑新生血管。
Purpose: Macular neovascularization is a relatively common and potentially visually devastating complication of age-related macular degeneration. In macular neovascularization, pathologic angiogenesis can originate from either the choroid or the retina, but we have limited understanding of how different cell types become dysregulated in this dynamic process.Methods: To study how gene expression is altered in focal areas of pathology, we performed spatial RNA sequencing on a human donor eye with macular neovascularization as well as a healthy control donor. We performed differential expression to identify genes enriched within the area of macular neovascularization and used deconvolution algorithms to predict the originating cell type of these dysregulated genes.Results: Within the area of neovascularization, endothelial cells demonstrated increased expression of genes related to Rho family GTPase signaling and integrin signaling. Likewise, VEGF and TGFB1 were identified as potential upstream regulators that could drive the observed gene expression changes produced by endothelial and retinal pigment epithelium cells in the macular neovascularization donor. These spatial gene expression profiles were compared to previous single-cell gene expression experiments in human age-related macular degeneration as well as a model of laser-induced neovascularization in mice. As a secondary aim, we investigated regional gene expression patterns within the macular neural retina and between the macular and peripheral choroid.Conclusions: Overall, this study spatially analyzes gene expression across the retina, retinal pigment epithelium, and choroid in health and describes a set of candidate molecules that become dysregulated in macular neovascularization.