美国芝加哥大学Nicolas Chevrier团队近期取得重要工作进展，他们研究提出将大幅面微阵列重新用于可扩展的空间转录组学。相关研究成果2024年11月19日在线发表于《自然—方法学》杂志上。

据介绍，空间分子分析是研究组织功能和故障的关键。然而，研究者目前还缺乏易于采用、成本低，且在样本量和数量方面可扩展的空间转录组学分析工具。

研究人员开发了一种方法，Array-seq，用于将经典寡核苷酸微阵列重新用于空间转录组学分析。研究人员从携带定制设计探针的微阵列中生成Array-seq载玻片，这些探针包含在已知坐标处独特条形码侧翼的常见序列。

然后，研究人员进行一个简单的两步反应，在微阵列上的所有点上产生mRNA捕获探针。使用小鼠组织的组织切片作为测试系统，Array-seq可以产生具有高检测灵敏度，和定位特异性的空间转录组。

此外，研究人员发现Array-seq载玻片的大表面积产生了空间转录组：（i）通过分析多器官切片以高通量产生，（ii）通过处理一个样本的连续切片以三维形式产生，以及（iii）在整个人体器官中产生。

因此，通过将经典DNA微阵列和下一代测序相结合，研究人员创建了一个简单灵活的平台，用于大规模的从小到大样本的空间分子研究。

附：英文原文

Title: Repurposing large-format microarrays for scalable spatial transcriptomics

Author: Cipurko, Denis, Ueda, Tatsuki, Mei, Linghan, Chevrier, Nicolas

Issue&Volume: 2024-11-19

Abstract: Spatiomolecular analyses are key to study tissue functions and malfunctions. However, we lack profiling tools for spatial transcriptomics that are easy to adopt, low cost and scalable in terms of sample size and number. Here, we describe a method, Array-seq, to repurpose classical oligonucleotide microarrays for spatial transcriptomics profiling. We generate Array-seq slides from microarrays carrying custom-design probes that contain common sequences flanking unique barcodes at known coordinates. Then we perform a simple, two-step reaction that produces mRNA capture probes across all spots on the microarray. We demonstrate that Array-seq yields spatial transcriptomes with high detection sensitivity and localization specificity using histological sections from mouse tissues as test systems. Moreover, we show that the large surface area of Array-seq slides yields spatial transcriptomes (i) at high throughput by profiling multi-organ sections, (ii) in three dimensions by processing serial sections from one sample, and (iii) across whole human organs. Thus, by combining classical DNA microarrays and next-generation sequencing, we have created a simple and flexible platform for spatiomolecular studies of small-to-large specimens at scale.

DOI: 10.1038/s41592-024-02501-5

Source: https://www.nature.com/articles/s41592-024-02501-5