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bioRxiv · 10.1101/2023.06.26.546618

Dendrimeric DNA Coordinate Barcoding Design for Spatial RNA Sequencing

Cao, J.·Zheng, Z.·Sun, D.·Chen, X.·Chen, R.·Lv, T.·An, Y.·Zheng, J.·Song, J.·Wu, L.·Yang, C.
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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 dendrimeric DNA coordinate barcoding design for spatial RNA sequencing (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/mm2). 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 10x Visium. Decoder-seq visualized a spatial single-cell atlas of mouse hippocampus at near-cellular resolution (15 m) 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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Cao, J., Zheng, Z., Sun, D., Chen, X., Chen, R., Lv, T., An, Y., Zheng, J., Song, J., Wu, L., Yang, C.. 2023-06-29. Dendrimeric DNA Coordinate Barcoding Design for Spatial RNA Sequencing. https://doi.org/10.1101/2023.06.26.546618

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