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Expansion sequencing: Spatially precise in situ transcriptomics in intact biological systems


Alon, Shahar; Goodwin, Daniel R; Sinha, Anubhav; Wassie, Asmamaw T; Chen, Fei; et al; IMAXT Consortium; Bodenmiller, Bernd; Kuett, L; Tietscher, S; Windhager, Jonas (2021). Expansion sequencing: Spatially precise in situ transcriptomics in intact biological systems. Science, 371(6528):eaax2656.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
07 Faculty of Science > Department of Quantitative Biomedicine
Dewey Decimal Classification:570 Life sciences; biology
Uncontrolled Keywords:Multidisciplinary
Language:English
Date:29 January 2021
Deposited On:01 Feb 2021 16:12
Last Modified:02 Feb 2021 09:21
Publisher:American Association for the Advancement of Science
ISSN:0036-8075
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1126/science.aax2656

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