计算生物学
转录组
条形码
DNA条形码
核糖核酸
生物
DNA
DNA测序
基因
计算机科学
遗传学
基因表达
进化生物学
操作系统
作者
Jian Cao,Zheng Zhong,Di Sun,Xin Chen,Rui Chen,Timchenko Lv,An Yu,Junhua Zheng,Jia Song,Lingling Wu,Chaoyong Yang
标识
DOI:10.1101/2023.06.26.546618
摘要
Abstract Spatially resolved transcriptomic technologies show promise in revealing complex pathophysiological processes, but developing sensitive, high-resolution, and cost-effective methodology is challenging. Here, we report a de ndrimeric DNA co ordinate barcoding de sign for spatial R NA seq uencing (Decoder-seq). This technology combined dendrimeric nano-substrates with microfluidic coordinate barcoding to generate high-density spatial DNA arrays with deterministically combinatorial barcodes in a resolution-flexible and cost-effective manner (∼$0.5/mm 2 ). Decoder-seq achieved high RNA capture efficiency, ∼68.9% that of in situ sequencing, and enhanced the detection of lowly expressed genes by ∼five-fold compared to 10× Visium. Decoder-seq visualized a spatial single-cell atlas of mouse hippocampus at near-cellular resolution (15 μm) and revealed dendrite-enriched mRNAs. Application to renal cancers dissected the heterogeneous tumor microenvironment of two subtypes, and identified spatial gradient expressed genes with the potential in predicting tumor prognosis and progression. Decoder-seq is compatible with sensitivity, resolution, and cost, making spatial transcriptomic analysis accessible to wider biomedical applications and researchers.
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