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Simultaneous CRISPR screening and spatial transcriptomics reveals intracellular, intercellular, and functional
Loϊc Binan1, Serwah Danquah1,2, Vera Valakh1,2
1Spatial Technology Platform, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Biorxiv : the Preprint Server for Biology
|December 11, 2023
Summary
Perturb-FISH combines imaging spatial transcriptomics with guide RNA detection to study gene function. This method reveals new insights into innate immunity and autism spectrum disorder risk genes at single-cell resolution.
Area of Science:
- Cell Biology
- Genomics
- Immunology
Background:
- Pooled optical screens offer large-scale cellular analysis but lack transcriptomic detail.
- Highly-plexed single-cell transcriptomics can inform molecular pathways but often lack spatial context.
Approach:
- Developed Perturb-FISH, integrating imaging spatial transcriptomics with in situ amplified guide RNA detection.
- Validated Perturb-FISH in lipopolysaccharide response screens, showing consistency with Perturb-seq intracellular effects.
- Applied Perturb-FISH to autism spectrum disorder risk genes, linking genetic interactions to functional phenotypes.
Key Points:
- Perturb-FISH enables massive-scale, single-cell resolution studies of gene function.
- Uncovered novel intercellular and density-dependent regulation in innate immune responses.
- Identified common calcium activity phenotypes and associated molecular pathways for ASD risk genes.
Conclusions:
- Perturb-FISH is a versatile method for dissecting genetic and molecular underpinnings of spatial and functional biology.
- Advances the study of complex biological systems by integrating transcriptomic, spatial, and functional data.
- Opens new avenues for understanding gene function in development, disease, and immunity.
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