Chromatin Potential Identified by Shared Single-Cell Profiling of RNA and Chromatin

© 2020 Elsevier Inc. Cell differentiation and function are regulated across multiple layers of gene regulation, including modulation of gene expression by changes in chromatin accessibility. However, differentiation is an asynchronous process precluding a temporal understanding of regulatory events...

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Main Authors: Ma, Sai, Zhang, Bing, LaFave, Lindsay M, Earl, Andrew S, Chiang, Zachary, Hu, Yan, Ding, Jiarui, Brack, Alison, Kartha, Vinay K, Tay, Tristan, Law, Travis, Lareau, Caleb, Hsu, Ya-Chieh, Regev, Aviv, Buenrostro, Jason D
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Language:English
Published: Elsevier BV 2021
Online Access:https://hdl.handle.net/1721.1/138197
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author Ma, Sai
Zhang, Bing
LaFave, Lindsay M
Earl, Andrew S
Chiang, Zachary
Hu, Yan
Ding, Jiarui
Brack, Alison
Kartha, Vinay K
Tay, Tristan
Law, Travis
Lareau, Caleb
Hsu, Ya-Chieh
Regev, Aviv
Buenrostro, Jason D
author2 Massachusetts Institute of Technology. Department of Biology
author_facet Massachusetts Institute of Technology. Department of Biology
Ma, Sai
Zhang, Bing
LaFave, Lindsay M
Earl, Andrew S
Chiang, Zachary
Hu, Yan
Ding, Jiarui
Brack, Alison
Kartha, Vinay K
Tay, Tristan
Law, Travis
Lareau, Caleb
Hsu, Ya-Chieh
Regev, Aviv
Buenrostro, Jason D
author_sort Ma, Sai
collection MIT
description © 2020 Elsevier Inc. Cell differentiation and function are regulated across multiple layers of gene regulation, including modulation of gene expression by changes in chromatin accessibility. However, differentiation is an asynchronous process precluding a temporal understanding of regulatory events leading to cell fate commitment. Here we developed simultaneous high-throughput ATAC and RNA expression with sequencing (SHARE-seq), a highly scalable approach for measurement of chromatin accessibility and gene expression in the same single cell, applicable to different tissues. Using 34,774 joint profiles from mouse skin, we develop a computational strategy to identify cis-regulatory interactions and define domains of regulatory chromatin (DORCs) that significantly overlap with super-enhancers. During lineage commitment, chromatin accessibility at DORCs precedes gene expression, suggesting that changes in chromatin accessibility may prime cells for lineage commitment. We computationally infer chromatin potential as a quantitative measure of chromatin lineage-priming and use it to predict cell fate outcomes. SHARE-seq is an extensible platform to study regulatory circuitry across diverse cells in tissues.
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spelling mit-1721.1/1381972023-12-08T17:01:16Z Chromatin Potential Identified by Shared Single-Cell Profiling of RNA and Chromatin Ma, Sai Zhang, Bing LaFave, Lindsay M Earl, Andrew S Chiang, Zachary Hu, Yan Ding, Jiarui Brack, Alison Kartha, Vinay K Tay, Tristan Law, Travis Lareau, Caleb Hsu, Ya-Chieh Regev, Aviv Buenrostro, Jason D Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT © 2020 Elsevier Inc. Cell differentiation and function are regulated across multiple layers of gene regulation, including modulation of gene expression by changes in chromatin accessibility. However, differentiation is an asynchronous process precluding a temporal understanding of regulatory events leading to cell fate commitment. Here we developed simultaneous high-throughput ATAC and RNA expression with sequencing (SHARE-seq), a highly scalable approach for measurement of chromatin accessibility and gene expression in the same single cell, applicable to different tissues. Using 34,774 joint profiles from mouse skin, we develop a computational strategy to identify cis-regulatory interactions and define domains of regulatory chromatin (DORCs) that significantly overlap with super-enhancers. During lineage commitment, chromatin accessibility at DORCs precedes gene expression, suggesting that changes in chromatin accessibility may prime cells for lineage commitment. We computationally infer chromatin potential as a quantitative measure of chromatin lineage-priming and use it to predict cell fate outcomes. SHARE-seq is an extensible platform to study regulatory circuitry across diverse cells in tissues. 2021-11-22T19:16:17Z 2021-11-22T19:16:17Z 2020 2021-11-22T19:11:07Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/138197 Ma, Sai, Zhang, Bing, LaFave, Lindsay M, Earl, Andrew S, Chiang, Zachary et al. 2020. "Chromatin Potential Identified by Shared Single-Cell Profiling of RNA and Chromatin." Cell, 183 (4). en 10.1016/J.CELL.2020.09.056 Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV PMC
spellingShingle Ma, Sai
Zhang, Bing
LaFave, Lindsay M
Earl, Andrew S
Chiang, Zachary
Hu, Yan
Ding, Jiarui
Brack, Alison
Kartha, Vinay K
Tay, Tristan
Law, Travis
Lareau, Caleb
Hsu, Ya-Chieh
Regev, Aviv
Buenrostro, Jason D
Chromatin Potential Identified by Shared Single-Cell Profiling of RNA and Chromatin
title Chromatin Potential Identified by Shared Single-Cell Profiling of RNA and Chromatin
title_full Chromatin Potential Identified by Shared Single-Cell Profiling of RNA and Chromatin
title_fullStr Chromatin Potential Identified by Shared Single-Cell Profiling of RNA and Chromatin
title_full_unstemmed Chromatin Potential Identified by Shared Single-Cell Profiling of RNA and Chromatin
title_short Chromatin Potential Identified by Shared Single-Cell Profiling of RNA and Chromatin
title_sort chromatin potential identified by shared single cell profiling of rna and chromatin
url https://hdl.handle.net/1721.1/138197
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