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Nature. 2019 Apr;568(7751):235-239. doi: 10.1038/s41586-019-1049-y. Epub 2019 Mar 25.

Transcriptome-scale super-resolved imaging in tissues by RNA seqFISH.

Author information

1
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA.
2
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
3
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard T.H.Chan School of Public Health, Boston, MA, USA.
4
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA. lcai@caltech.edu.

Abstract

Imaging the transcriptome in situ with high accuracy has been a major challenge in single-cell biology, which is particularly hindered by the limits of optical resolution and the density of transcripts in single cells1-5. Here we demonstrate an evolution of sequential fluorescence in situ hybridization (seqFISH+). We show that seqFISH+ can image mRNAs for 10,000 genes in single cells-with high accuracy and sub-diffraction-limit resolution-in the cortex, subventricular zone and olfactory bulb of mouse brain, using a standard confocal microscope. The transcriptome-level profiling of seqFISH+ allows unbiased identification of cell classes and their spatial organization in tissues. In addition, seqFISH+ reveals subcellular mRNA localization patterns in cells and ligand-receptor pairs across neighbouring cells. This technology demonstrates the ability to generate spatial cell atlases and to perform discovery-driven studies of biological processes in situ.

Comment in

PMID:
30911168
PMCID:
PMC6544023
[Available on 2019-09-25]
DOI:
10.1038/s41586-019-1049-y

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