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High-throughput single-cell chromatin accessibility CRISPR screens enable unbiased identification of regulatory networks in cancer

Sarah E. Pierce, Jeffrey M. Granja and William J. Greenleaf ()
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Sarah E. Pierce: Stanford University School of Medicine
Jeffrey M. Granja: Stanford University School of Medicine
William J. Greenleaf: Stanford University School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-8

Abstract: Abstract Chromatin accessibility profiling can identify putative regulatory regions genome wide; however, pooled single-cell methods for assessing the effects of regulatory perturbations on accessibility are limited. Here, we report a modified droplet-based single-cell ATAC-seq protocol for perturbing and evaluating dynamic single-cell epigenetic states. This method (Spear-ATAC) enables simultaneous read-out of chromatin accessibility profiles and integrated sgRNA spacer sequences from thousands of individual cells at once. Spear-ATAC profiling of 104,592 cells representing 414 sgRNA knock-down populations reveals the temporal dynamics of epigenetic responses to regulatory perturbations in cancer cells and the associations between transcription factor binding profiles.

Date: 2021
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DOI: 10.1038/s41467-021-23213-w

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