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通过空间转录组学对 Stanford A 型主动脉夹层组织切片中的基因表达进行可视化和分析。

Visualization and Analysis of Gene Expression in Stanford Type A Aortic Dissection Tissue Section by Spatial Transcriptomics.

作者信息

Li Yan-Hong, Cao Ying, Liu Fen, Zhao Qian, Adi Dilare, Huo Qiang, Liu Zheng, Luo Jun-Yi, Fang Bin-Bin, Tian Ting, Li Xiao-Mei, Liu Di, Yang Yi-Ning

机构信息

Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.

Department of Clinical Laboratory, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.

出版信息

Front Genet. 2021 Jun 28;12:698124. doi: 10.3389/fgene.2021.698124. eCollection 2021.

Abstract

Spatial transcriptomics enables gene expression events to be pinpointed to a specific location in biological tissues. We developed a molecular approach for low-cell and high-fiber Stanford type A aortic dissection and preliminarily explored and visualized the heterogeneity of ascending aortic types and mapping cell-type-specific gene expression to specific anatomical domains. We collected aortic samples from 15 patients with Stanford type A aortic dissection and a case of ascending aorta was randomly selected followed by 10x Genomics and spatial transcriptomics sequencing. In data processing of normalization, component analysis and dimensionality reduction analysis, different algorithms were compared to establish the pipeline suitable for human aortic tissue. We identified 19,879 genes based on the count level of gene expression at different locations and they were divided into seven groups based on gene expression trends. Major cell that the population may contain are indicated, and we can find different main distribution of different cell types, among which the tearing sites were mainly macrophages and stem cells. The gene expression of these different locations and the cell types they may contain are correlated and discussed in terms of their involvement in immunity, regulation of oxygen homeostasis, regulation of cell structure and basic function. This approach provides a spatially resolved transcriptome- and tissue-wide perspective of the adult human aorta and will allow the application of human fibrous aortic tissues without any effect on genes in different layers with low RNA expression levels. Our findings will pave the way toward both a better understanding of Stanford type A aortic dissection pathogenesis and heterogeneity and the implementation of more effective personalized therapeutic approaches.

摘要

空间转录组学能够将基因表达事件定位到生物组织中的特定位置。我们开发了一种针对低细胞数和高纤维含量的斯坦福A型主动脉夹层的分子方法,并初步探索并可视化了升主动脉类型的异质性,以及将细胞类型特异性基因表达映射到特定的解剖区域。我们收集了15例斯坦福A型主动脉夹层患者的主动脉样本,并随机选取1例升主动脉样本进行10x基因组学和空间转录组学测序。在归一化、成分分析和降维分析的数据处理过程中,比较了不同的算法,以建立适合人类主动脉组织的流程。我们根据不同位置基因表达的计数水平鉴定出19879个基因,并根据基因表达趋势将它们分为七组。指出了该群体可能包含的主要细胞类型,我们可以发现不同细胞类型的不同主要分布,其中撕裂部位主要是巨噬细胞和干细胞。讨论了这些不同位置的基因表达及其可能包含的细胞类型之间的相关性,以及它们在免疫、氧稳态调节、细胞结构调节和基本功能方面的作用。这种方法提供了成人人类主动脉在空间上解析的转录组和全组织视角,并将允许应用人类纤维性主动脉组织,而不会对低RNA表达水平的不同层中的基因产生任何影响。我们的研究结果将为更好地理解斯坦福A型主动脉夹层的发病机制和异质性以及实施更有效的个性化治疗方法铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e22/8275070/99237f146efb/fgene-12-698124-g001.jpg

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