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

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 ev...

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Autores principales: Pierce, Sarah E., Granja, Jeffrey M., Greenleaf, William J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137922/
https://www.ncbi.nlm.nih.gov/pubmed/34016988
http://dx.doi.org/10.1038/s41467-021-23213-w
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author Pierce, Sarah E.
Granja, Jeffrey M.
Greenleaf, William J.
author_facet Pierce, Sarah E.
Granja, Jeffrey M.
Greenleaf, William J.
author_sort Pierce, Sarah E.
collection PubMed
description 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.
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spelling pubmed-81379222021-06-03 High-throughput single-cell chromatin accessibility CRISPR screens enable unbiased identification of regulatory networks in cancer Pierce, Sarah E. Granja, Jeffrey M. Greenleaf, William J. Nat Commun Article 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. Nature Publishing Group UK 2021-05-20 /pmc/articles/PMC8137922/ /pubmed/34016988 http://dx.doi.org/10.1038/s41467-021-23213-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Pierce, Sarah E.
Granja, Jeffrey M.
Greenleaf, William J.
High-throughput single-cell chromatin accessibility CRISPR screens enable unbiased identification of regulatory networks in cancer
title High-throughput single-cell chromatin accessibility CRISPR screens enable unbiased identification of regulatory networks in cancer
title_full High-throughput single-cell chromatin accessibility CRISPR screens enable unbiased identification of regulatory networks in cancer
title_fullStr High-throughput single-cell chromatin accessibility CRISPR screens enable unbiased identification of regulatory networks in cancer
title_full_unstemmed High-throughput single-cell chromatin accessibility CRISPR screens enable unbiased identification of regulatory networks in cancer
title_short High-throughput single-cell chromatin accessibility CRISPR screens enable unbiased identification of regulatory networks in cancer
title_sort high-throughput single-cell chromatin accessibility crispr screens enable unbiased identification of regulatory networks in cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137922/
https://www.ncbi.nlm.nih.gov/pubmed/34016988
http://dx.doi.org/10.1038/s41467-021-23213-w
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