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Expansion sequencing: Spatially precise in situ transcriptomics in intact biological systems
Name
nihms-1670746.pdf
Description
Accepted version
Size
1.65 MB
Format
Adobe PDF
Checksum (MD5)
540d49f79b40f5ac0571032dc76b831b
Date Issued
2021
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Version
Author's final manuscript
Abstract
Methods for highly multiplexed RNA imaging are limited in spatial resolution and thus in their ability to localize transcripts to nanoscale and subcellular compartments. We adapt expansion microscopy, which physically expands biological specimens, for long-read untargeted and targeted in situ RNA sequencing. We applied untargeted expansion sequencing (ExSeq) to the mouse brain, which yielded the readout of thousands of genes, including splice variants. Targeted ExSeq yielded nanoscale-resolution maps of RNAs throughout dendrites and spines in the neurons of the mouse hippocampus, revealing patterns across multiple cell types, layer-specific cell types across the mouse visual cortex, and the organization and position-dependent states of tumor and immune cells in a human metastatic breast cancer biopsy. Thus, ExSeq enables highly multiplexed mapping of RNAs from nanoscale to system scale.
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
10.1126/science.aax2656
