Perturb-Multimodal: A platform for pooled genetic screens with imaging and sequencing in intact mammalian tissue.

ABSTRACT: Metazoan life requires the coordinated activities of thousands of genes in spatially organized cell types. Understanding the basis of tissue function requires approaches to dissect the genetic control of diverse cellular and tissue phenotypes in vivo. Here, we present Perturb-Multimodal (Perturb-Multi), a paired imaging and sequencing method to construct large-scale, multimodal genotype-phenotype maps in tissues with pooled genetic perturbations. Using imaging, we identify perturbations in individual cells while simultaneously measuring their gene expression profiles and subcellular morphology. Using single-cell sequencing, we measure full transcriptomic responses to the same perturbations. We apply Perturb-Multi to study hundreds of genetic perturbations in the mouse liver. Our data sugge

SUBMITTER: Saunders RA 

PROVIDER: S-EPMC12324982 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature