美国康奈尔大学Iwijn De Vlaminck和Benjamin D. Cosgrove共同合作近期取得重要工作进展，他们研究提出可以通过原位多腺苷酸化绘制全转录组空间分布图谱。相关研究工作2022年11月3日在线发表于《自然—生物技术》杂志。

研究人员发现RNA的酶促原位聚腺苷酸化能够检测RNA的全谱，从而将基于测序的空间转录组学的范围扩展到整个转录组。研究人员证明了空间总RNA测序（STRS）方法捕获编码RNA、非编码RNA和病毒RNA，并应用STRS研究骨骼肌再生和病毒性心肌炎。

他们分析揭示了具有近细胞分辨率的非编码RNA表达的空间模式，确定了骨骼肌再生中非编码转录物的空间定义表达，并强调了与局部病毒RNA丰度相关的宿主转录反应。STRS只需要在10x Genomics广泛使用的Visium空间总RNA测序协议中增加一步，因此可以很容易地被采用，从而为空间基因调控和生物学提供新的见解。

据了解，空间转录组学揭示了基因表达的空间背景，但目前的方法仅限于分析多聚腺苷（A尾）RNA转录本。

附：英文原文

Title: Spatial mapping of the total transcriptome by in situ polyadenylation

Author: McKellar, David W., Mantri, Madhav, Hinchman, Meleana M., Parker, John S. L., Sethupathy, Praveen, Cosgrove, Benjamin D., De Vlaminck, Iwijn

Issue&Volume: 2022-11-03

Abstract: Spatial transcriptomics reveals the spatial context of gene expression, but current methods are limited to assaying polyadenylated (A-tailed) RNA transcripts. Here we demonstrate that enzymatic in situ polyadenylation of RNA enables detection of the full spectrum of RNAs, expanding the scope of sequencing-based spatial transcriptomics to the total transcriptome. We demonstrate that our spatial total RNA-sequencing (STRS) approach captures coding RNAs, noncoding RNAs and viral RNAs. We apply STRS to study skeletal muscle regeneration and viral-induced myocarditis. Our analyses reveal the spatial patterns of noncoding RNA expression with near-cellular resolution, identify spatially defined expression of noncoding transcripts in skeletal muscle regeneration and highlight host transcriptional responses associated with local viral RNA abundance. STRS requires adding only one step to the widely used Visium spatial total RNA-sequencing protocol from 10x Genomics, and thus could be easily adopted to enable new insights into spatial gene regulation and biology.

DOI: 10.1038/s41587-022-01517-6

Source: https://www.nature.com/articles/s41587-022-01517-6