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bioRxivGenomicsPreprint

In vivo multiomic Perturb-seq with enhanced nuclear gRNA capture

Xinhe ZhengiD, Jiwen LiiD, Kwanho KimiD, Sean SimmonsiD, Ziyan Zhao, Melodi TastemeliD, Nhan HuynhiD, Huixian Qiu, Juntong Ye, Cassandra M WhteiD, Joshua Z. LeviniD, Xin JiniD

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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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