High-throughput profiling of in situ gene expression represents a major advance towards the systematic understanding of tissue complexity. Applied with enough capture area and high sample throughput it will help to define the spatio-temporal dynamics of gene expression in tissues and organisms. Yet, current technologies have considerable bottlenecks that limit widespread application. Here, we have combined DNA nanoball (DNB) patterned array chips and in situ RNA capture to develop Stereo-seq (Spatio-Temporal Enhanced REsolution Omics-sequencing). This approach allows high sample throughput transcriptomic profiling of histological sections at unprecedented (nanoscale) resolution with areas expandable to centimeter scale, high sensitivity and homogenous capture rate. As proof of principle, we applied Stereo-seq to the adult mouse brain and sagittal sections of E11.5 and E16.5 mouse embryos. Thanks to its unique features and amenability to additional modifications, Stereo-seq can pave the way for the systematic spatially resolved-omics characterization of tissues and organisms.
原位基因表达的高通量分析是系统理解组织复杂性的一个重大进展。应用足够的捕获面积和高的样本吞吐量，它将有助于定义基因表达在组织和生物的时空动态。然而，目前的技术存在相当大的瓶颈，限制了其广泛应用。在这里，我们将DNA纳米球(DNB)模式阵列芯片和原位RNA捕获相结合，开发了Stereo-seq(时空增强分辨率组学-测序)。这种方法能够以前所未有的(纳米级)分辨率对组织切片进行高样品通量转录组分析，面积可扩展到厘米级，高灵敏度和均匀捕获率。作为原理证明，我们将Stereo-seq应用于成年小鼠大脑和E11.5和E16.5小鼠胚胎的矢状切片。由于其独特的特性和可修饰性，Stereo-seq可以为组织和生物的系统空间解析组学表征铺平道路。
