In vivo multiomic Perturb-seq with enhanced nuclear gRNA capture
Zheng, X.; Li, J.; Kim, K.; Simmons, S. K.; Zhao, Z.; Tastemel, M.; Huynh, N.; Qiu, H.; Ye, J.; Whte, C. M.; Levin, J. Z.; Jin, X.
Show abstract
In vivo CRISPR screening with joint transcriptomic and chromatin readouts has been limited by inefficient recovery of gRNAs from nuclei. Here, we developed in vivo multiomic Perturb-seq, an effective platform combining nuclear transcript anchoring with gRNA-specific capture and amplification to enable high-fidelity, high-recovery gRNA assignment and scalable perturbation-resolved single-nucleus multiomics. Applying this platform to interrogate neurodevelopmental disorder risk genes in the developing cortex reveals cell-type-specific transcriptomic and epigenomic perturbation phenotypes.
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