Yan Rachel E, Corman Alba, Katgara Lyla, Wang Xiao, Xue Xinhe, Gajic Zoran Z, Sam Richard, Farid Michael, Friedman Samuel M, Choo Jungwook, Raimondi Ivan, Ganesan Shridar, Katsevich Eugene, Greenfield Jeffrey P, Dahmane Nadia, Sanjana Neville E
New York Genome Center, New York, NY, USA.
Department of Biology, New York University, New York, NY, USA.
Nat Biotechnol. 2024 Nov 21. doi: 10.1038/s41587-024-02475-x.
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.
汇集式单细胞CRISPR筛选已对基因表达或染色质可及性进行了分析，但未同时分析这两种模式。在此，我们开发了MultiPerturb-seq，这是一种高通量CRISPR筛选平台，它通过组合索引结合微滴微流控技术，实现了联合单核染色质可及性、转录组和向导RNA捕获，从而扩大通量并整合所有三种模式。我们在一种罕见的儿科癌症中鉴定出关键的分化基因，并确定ZNHIT1作为癌症重编程治疗的潜在靶点。
