Journal
NATURE
Volume 568, Issue 7751, Pages 235-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41586-019-1049-y
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Funding
- NIH [TR01 OD024686]
- NIH HubMAP [UG3HL145609]
- Paul G. Allen Frontiers Foundation Discovery Center
- Chan-Zuckerberg Initiative pilot grant
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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 cells(1-5). 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.
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