Journal
SCIENCE
Volume 361, Issue 6400, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aat5691
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Funding
- Life Science Research Foundation fellowship
- Gordon and Betty Moore Foundation
- Fannie and John Hertz Foundation Fellowship
- NSF Graduate Research Fellowship
- NIMH Ruth L. Kirschstein NRSA fellowship [1F32MH110144-01]
- NIMH Career Development Award [1K08MH113039]
- Bio-X Interdisciplinary Initiatives Seed Grant
- Parker Institute for Cancer Immunotherapy
- FDA
- NIH
- Human Frontiers Science Program
- NIMH [R01MH099647]
- NIDA [P50DA042012]
- DARPA NeuroFAST program [W911NF-14-2-0013]
- NSF NeuroNex program
- Gatsby Foundation
- AE Foundation
- NOMIS Foundation
- Fresenius Foundation
- Wiegers Family Fund
- James Grosfeld Foundation
- Sam and Betsy Reeves Foundation
- H.L. Snyder Foundation
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Retrieving high-content gene-expression information while retaining three-dimensional (3D) positional anatomy at cellular resolution has been difficult, limiting integrative understanding of structure and function in complex biological tissues. We developed and applied a technology for 3D intact-tissue RNA sequencing, termed STARmap (spatially-resolved transcript amplicon readout mapping), which integrates hydrogel-tissue chemistry. targeted signal amplification, and in situ sequencing. The capabilities of STARmap were tested by mapping 160 to 1020 genes simultaneously in sections of mouse brain at single-cell resolution with high efficiency, accuracy, and reproducibility. Moving to thick tissue blocks, we observed a molecularly defined gradient distribution of excitatory-neuron subtypes across cubic millimeter-scale volumes (>30,000 cells) and a short-range 3D self-clustering in many inhibitory-neuron subtypes that could be identified and described with 3D STARmap.
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