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bioRxiv · 10.1101/2022.12.11.519542

Sequencing-free Tissue-wide Spatial Profiling of Post-transcriptional Regulations

Ji, X.·Fang, P.·Zhao, X.·Xiong, C.·Yang, Q.·Wan, Y.·Yan Do, R.·Wang, Z.·Qi, L.·Huang, L.·Zhang, W.·Wang, X.·Shi, P.
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Abstract

The importance of genetic or epi-genetic heterogeneity has been increasingly recognized, but it has been challenging to profile intracellular post-transcriptional targets with sufficient throughput and resolution at across large-scale tissue samples. This study describes a technique, Spectrum-FISH, for high-throughput, sequencing-free, and tissue-wide spatial profiling of various post-transcriptional targets in acute tissue sections with subcellular resolution. The platform uses a biochip with an array of vertically aligned nanoprobes to effectively extract intracellular molecules for downstream analysis in the coordinates of the large-scale of cells within a tissue slice. As a proof-of-concept, the Spectrum-FISH is used to profile the spatial dynamics of 24 miRNAs and 9 m6A-modified messenger RNAs (m6A-mRNA) in acute olfactory bulb (OB) slices of millimeter scale. The results showed potentially multiomics spatial heterogeneity for the examined post-transcriptional regulations in rodent OB, especially in the outer plexiform layer and granule layer, where highly correlated miRNAs and m6A-mRNAs groups were identified, indicating a potential cooperative involvement of different post-transcriptional regulations at these OB regions.

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Ji, X., Fang, P., Zhao, X., Xiong, C., Yang, Q., Wan, Y., Yan Do, R., Wang, Z., Qi, L., Huang, L., Zhang, W., Wang, X., Shi, P.. 2022-12-13. Sequencing-free Tissue-wide Spatial Profiling of Post-transcriptional Regulations. https://doi.org/10.1101/2022.12.11.519542

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