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

IF 33.1 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Nature biotechnology Pub Date : 2024-11-21 DOI:10.1038/s41587-024-02475-x

Rachel E. Yan, Alba Corman, Lyla Katgara, Xiao Wang, Xinhe Xue, Zoran Z. Gajic, Richard Sam, Michael Farid, Samuel M. Friedman, Jungwook Choo, Ivan Raimondi, Shridar Ganesan, Eugene Katsevich, Jeffrey P. Greenfield, Nadia Dahmane, Neville E. Sanjana

引用次数: 0

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.

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联合单核染色质可及性和转录组图谱的集合 CRISPR 筛选

汇集的单细胞 CRISPR 筛选可以分析基因表达或染色质可及性，但不能同时分析两种模式。在这里，我们开发了MultiPerturb-seq，这是一种高通量CRISPR筛选平台，利用组合索引技术和液滴微流控技术联合捕获单核染色质可及性、转录组和引导RNA，以提高通量并整合所有三种模式。我们确定了一种罕见儿科癌症的关键分化基因，并将 ZNHIT1 确立为癌症重编程疗法的潜在靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature biotechnology 工程技术-生物工程与应用微生物

CiteScore

63.00

自引率

1.70%

发文量

382

审稿时长

3 months

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