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003-Perturb-Multimodal Imaging and Sequencing

This resource article introduces Perturb-Multimodal (Perturb-Multi), an innovative platform integrating imaging and sequencing for pooled genetic screening in intact mammalian tissues. The method captures in situ genotypes and multiple RNA-protein phenotypes through RCA-MERFISH, and enables in vivo CRISPR screening while preserving complete transcriptomes through fixed-cell Perturb-seq. The article elaborates on these technical innovations, using mouse liver as an example to demonstrate applications in exploring genetic regulation of liver function, cellular zonation, stress responses, and…

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