上海交通大学杨朝勇等研究人员合作发现，Decoder-seq可提高空间RNA测序的mRNA捕获效率。该项研究成果于2024年1月16日在线发表在《自然—生物技术》杂志上。

研究人员报告了一种用于空间RNA测序的树枝状DNA坐标条形码设计（Decoder-seq），它具有高灵敏度和高分辨率。Decoder-seq将树枝状纳米基底与微流体坐标条形码相结合，生成的空间阵列DNA密度比以前报道的方法高出约十倍，同时保持了分辨率的灵活性。研究表明，Decoder-seq的高RNA捕获效率提高了对小鼠嗅球中低表达的嗅觉受体（Olfr）基因的检测，并有助于发现两个Olfr基因的独特层富集模式。

Decoder-seq提供的近细胞分辨率帮助构建了小鼠海马的空间单细胞图谱，揭示了神经元中树突丰富的mRNA。将Decoder-seq应用于人类肾细胞癌时，研究人员剖析了不同癌症亚型的异质性肿瘤微环境，并确定了与上皮-间质转化相关的空间梯度表达基因，这些基因具有预测肿瘤预后和进展的潜力。

研究人员表示，高分辨率的空间转录组学技术在mRNA检测方面往往缺乏高灵敏度。

附：英文原文

Title: Decoder-seq enhances mRNA capture efficiency in spatial RNA sequencing

Author: Cao, Jiao, Zheng, Zhong, Sun, Di, Chen, Xin, Cheng, Rui, Lv, Tianpeng, An, Yu, Zheng, Junhua, Song, Jia, Wu, Lingling, Yang, Chaoyong

Issue&Volume: 2024-01-16

Abstract: Spatial transcriptomics technologies with high resolution often lack high sensitivity in mRNA detection. Here we report a dendrimeric DNA coordinate barcoding design for spatial RNA sequencing (Decoder-seq), which offers both high sensitivity and high resolution. Decoder-seq combines dendrimeric nanosubstrates with microfluidic coordinate barcoding to generate spatial arrays with a DNA density approximately ten times higher than previously reported methods while maintaining flexibility in resolution. We show that the high RNA capture efficiency of Decoder-seq improved the detection of lowly expressed olfactory receptor (Olfr) genes in mouse olfactory bulbs and contributed to the discovery of a unique layer enrichment pattern for two Olfr genes. The near-cellular resolution provided by Decoder-seq has enabled the construction of a spatial single-cell atlas of the mouse hippocampus, revealing dendrite-enriched mRNAs in neurons. When applying Decoder-seq to human renal cell carcinomas, we dissected the heterogeneous tumor microenvironment across different cancer subtypes and identified spatial gradient-expressed genes related to epithelial–mesenchymal transition with the potential to predict tumor prognosis and progression.

DOI: 10.1038/s41587-023-02086-y

Source: https://www.nature.com/articles/s41587-023-02086-y