A genome-scale single-cell CRISPRi map of trans gene regulation across human pluripotent stem cell lines

Population-scale resources of genetic, molecular, and cellular information form the basis for understanding human genomes, charting the heritable basis of disease and tracing the effects of mutations. Pooled perturbation assays, probing the effect of many perturbations coupled with single-cell RNA sequencing (scRNA-seq) readout, are especially potent references for interpreting disease-linked mutations or gene-expression changes. However, the utility of existing maps has been limited by the comprehensiveness of perturbations conducted and the relevance of their cell-line context. Here, we present a genome-scale CRISPR interference perturbation map with scRNA-seq readout across many genetic backgrounds in human pluripotent cells. We map trans expression changes induced by knockdowns and characterize their variation across donors, with expression quantitative trait loci linked to higher genetic modulation of perturbation effects. This study pioneers population-scale CRISPR perturbations with high-dimensional readouts, which will fuel the future of effective modulation of cellular disease phenotypes.

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Publication Details

Journal
Cell Genomics
Published
2025-12-01
DOI
https://doi.org/10.1016/j.xgen.2025.101076
Primary Topic
CRISPR and Genetic Engineering
Type
article
Field-Weighted Citation Impact
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article

A genome-scale single-cell CRISPRi map of trans gene regulation across human pluripotent stem cell lines

Magdalena E Strauß, Marc Jan Bonder, Andrew Bassett, Steven Leonard et al.
Cell Genomics
CRISPR and Genetic Engineering
article

A genome-scale single-cell CRISPRi map of trans gene regulation across human pluripotent stem cell lines

Magdalena E Strauß, Marc Jan Bonder, Andrew Bassett, Steven Leonard, Claudia Feng, Jana M. Braunger, Jing Su, Britta Velten, Edgar Garriga Nogales, Leopold Parts, Alistair S. Dunham, David F. Burke, Daniele Muraro, Elin Madli Peets, Sunay Usluer, Oliver Stegle, Kimberly Ai Xian Cheam, Luca Crepaldi, Yan Zhou, Sarah Cooper, Yong Gu, Bo Fussing
article en

Abstract

Population-scale resources of genetic, molecular, and cellular information form the basis for understanding human genomes, charting the heritable basis of disease and tracing the effects of mutations. Pooled perturbation assays, probing the effect of many perturbations coupled with single-cell RNA sequencing (scRNA-seq) readout, are especially potent references for interpreting disease-linked mutations or gene-expression changes. However, the utility of existing maps has been limited by the comprehensiveness of perturbations conducted and the relevance of their cell-line context. Here, we present a genome-scale CRISPR interference perturbation map with scRNA-seq readout across many genetic backgrounds in human pluripotent cells. We map trans expression changes induced by knockdowns and characterize their variation across donors, with expression quantitative trait loci linked to higher genetic modulation of perturbation effects. This study pioneers population-scale CRISPR perturbations with high-dimensional readouts, which will fuel the future of effective modulation of cellular disease phenotypes.

Cell GenomicsVol. 6(2)
European Bioinformatics Institute (GB), German Cancer Research Center (DE), King's College London (GB), Heidelberg University (DE), Wellcome Sanger Institute (GB), DKFZ-ZMBH Alliance (DE)
Openalex Percentile: Top 66%
CRISPR and Genetic Engineering
DOIOpen Access PDFOpenAlex
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