Positional influence on cellular transcriptional identity revealed through spatially segmented single-cell transcriptomics.

IF 9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Systems Pub Date : 2023-06-21 DOI:10.1016/j.cels.2023.05.003

David B Morse, Aleksandra M Michalowski, Michele Ceribelli, Joachim De Jonghe, Maria Vias, Deanna Riley, Theresa Davies-Hill, Ty Voss, Stefania Pittaluga, Christoph Muus, Jiamin Liu, Samantha Boyle, David A Weitz, James D Brenton, Jason D Buenrostro, Tuomas P J Knowles, Craig J Thomas

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引用次数: 0

Abstract

Single-cell RNA sequencing (scRNA-seq) is a powerful technique for describing cell states. Identifying the spatial arrangement of these states in tissues remains challenging, with the existing methods requiring niche methodologies and expertise. Here, we describe segmentation by exogenous perfusion (SEEP), a rapid and integrated method to link surface proximity and environment accessibility to transcriptional identity within three-dimensional (3D) disease models. The method utilizes the steady-state diffusion kinetics of a fluorescent dye to establish a gradient along the radial axis of disease models. Classification of sample layers based on dye accessibility enables dissociated and sorted cells to be characterized by transcriptomic and regional identities. Using SEEP, we analyze spheroid, organoid, and in vivo tumor models of high-grade serous ovarian cancer (HGSOC). The results validate long-standing beliefs about the relationship between cell state and position while revealing new concepts regarding how spatially unique microenvironments influence the identity of individual cells within tumors.

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通过空间分割的单细胞转录组学揭示了位置对细胞转录特性的影响。

单细胞RNA测序（scRNA-seq）是一种描述细胞状态的强大技术。确定这些状态在组织中的空间排列仍然具有挑战性，现有的方法需要利基方法和专业知识。在这里，我们描述了通过外源性灌注（SEEP）进行分割，这是一种在三维（3D）疾病模型中将表面接近性和环境可及性与转录特性联系起来的快速综合方法。该方法利用荧光染料的稳态扩散动力学来建立沿着疾病模型的径向轴的梯度。基于染料可及性的样品层分类使解离和分选的细胞能够通过转录组和区域身份进行表征。使用SEEP，我们分析了高级别浆液性癌症（HGSOC）的球体、类器官和体内肿瘤模型。该结果验证了关于细胞状态和位置之间关系的长期信念，同时揭示了关于空间独特的微环境如何影响肿瘤内单个细胞身份的新概念。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Systems Medicine-Pathology and Forensic Medicine

CiteScore

16.50

自引率

1.10%

发文量

审稿时长

42 days

期刊介绍： In 2015, Cell Systems was founded as a platform within Cell Press to showcase innovative research in systems biology. Our primary goal is to investigate complex biological phenomena that cannot be simply explained by basic mathematical principles. While the physical sciences have long successfully tackled such challenges, we have discovered that our most impactful publications often employ quantitative, inference-based methodologies borrowed from the fields of physics, engineering, mathematics, and computer science. We are committed to providing a home for elegant research that addresses fundamental questions in systems biology.