Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Oct;43(10):1628-1634.
doi: 10.1038/s41587-024-02475-x. Epub 2024 Nov 21.

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

Rachel E Yan  1   2   3   4 , Alba Corman  1   2 , Lyla Katgara  1   2 , Xiao Wang  1   2 , Xinhe Xue  1   2 , Zoran Z Gajic  1   2 , Richard Sam  1   2 , Michael Farid  1   2 , Samuel M Friedman  1   2 , Jungwook Choo  1   2 , Ivan Raimondi  1   5 , Shridar Ganesan  3 , Eugene Katsevich  6 , Jeffrey P Greenfield  4 , Nadia Dahmane  4 , Neville E Sanjana  7   8
Affiliations

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

Rachel E Yan et al. Nat Biotechnol. 2025 Oct.

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.

PubMed Disclaimer

Conflict of interest statement

Competing interests: The New York Genome Center and New York University have applied for patents related to the work in this article. N.E.S. is an adviser to Qiagen and a cofounder and adviser of TruEdit Bio and OverT Bio. The other authors declare no competing interests.

References

    1. Dixit, A. et al. Perturb-Seq: dissecting molecular circuits with scalable single-cell RNA profiling of pooled genetic screens. Cell 167, 1853–1866.e17 (2016).
    1. Replogle, J. M. et al. Mapping information-rich genotype–phenotype landscapes with genome-scale Perturb-seq. Cell 185, 2559–2575.e28 (2022).
    1. Frangieh, C. J. et al. Multimodal pooled Perturb-CITE-seq screens in patient models define mechanisms of cancer immune evasion. Nat. Genet. 53, 332–341 (2021). - PubMed - PMC - DOI
    1. Mimitou, E. P. et al. Multiplexed detection of proteins, transcriptomes, clonotypes and CRISPR perturbations in single cells. Nat. Methods 16, 409–412 (2019). - PubMed - PMC - DOI
    1. Rubin, A. J. et al. Coupled single-cell CRISPR screening and epigenomic profiling reveals causal gene regulatory networks. Cell 176, 361–376.e17 (2019).

MeSH terms