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Pooled CRISPR screens with joint single-nucleus chromatin accessibility and transcriptome profiling

Nat Biotechnol. 2024 Nov 21. doi: 10.1038/s41587-024-02475-x. Online ahead of print.

ABSTRACT

Pooled single-cell CRISPR screens have profiled either gene expression or chromatin accessibility but not both modalities. Here we develop MultiPerturb-seq, a high-throughput CRISPR screening platform with joint single-nucleus chromatin accessibility, transcriptome and guide RNA capture using combinatorial indexing combined with droplet microfluidics to scale throughput and integrate all three modalities. We identify key differentiation genes in a rare pediatric cancer and establish ZNHIT1 as a potential target for cancer reprogramming therapy.

PMID:39572737 | DOI:10.1038/s41587-024-02475-x

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