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

Yan, Rachel E; Corman, Alba; Katgara, Lyla; Wang, Xiao; Xue, Xinhe; Gajic, Zoran Z; Sam, Richard; Farid, Michael et al. · Nat Biotechnol · 2025

basic_science · Level V

Where this comes from

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.

Medical subject headings