In vivo multiomic Perturb-seq with enhanced nuclear gRNA capture.

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Publication Year:
2026
Authors:
Xinhe Zheng, Jiwen Li, Kwanho Kim, Sean K Simmons, Ziyan Zhao, Melodi Tastemel, Nhan Huynh, Huixian Qiu, Juntong Ye, Cassandra M White, Joshua Z Levin, Xin Jin
PubMed ID:
41889810
Funding Grants:
Public Summary:
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.
Scientific 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.