Context specificity of the EMT transcriptional response
Epithelial–mesenchymal plasticity contributes to many biological processes, including tumor progression. Various epithelial–mesenchymal transition (EMT) responses have been reported and no common, EMT-defining gene expression program has been identified. Here, we have performed a comparative analysi...
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| Published in: | Nature communications Vol. 11; no. 1; pp. 2142 - 9 |
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| Main Authors: | , |
| Format: | Journal Article |
| Language: | English |
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Nature Publishing Group UK
01.05.2020
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| ISSN: | 2041-1723, 2041-1723 |
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| Abstract | Epithelial–mesenchymal plasticity contributes to many biological processes, including tumor progression. Various epithelial–mesenchymal transition (EMT) responses have been reported and no common, EMT-defining gene expression program has been identified. Here, we have performed a comparative analysis of the EMT response, leveraging highly multiplexed single-cell RNA sequencing (scRNA-seq) to measure expression profiles of 103,999 cells from 960 samples, comprising 12 EMT time course experiments and independent kinase inhibitor screens for each. We demonstrate that the EMT is vastly context specific, with an average of only 22% of response genes being shared between any two conditions, and over half of all response genes were restricted to 1–2 time course experiments. Further, kinase inhibitor screens revealed signaling dependencies and modularity of these responses. These findings suggest that the EMT is not simply a single, linear process, but is highly variable and modular, warranting quantitative frameworks for understanding nuances of the transition.
It is unclear if a common EMT expression program exists. Here, the authors perform multiplexed single-cell RNA sequencing across 12 EMT time courses and 16 kinase inhibitor screens, and find that EMT transcriptional responses are context specific and EMT is not a single, linear transition. |
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| AbstractList | Epithelial-mesenchymal plasticity contributes to many biological processes, including tumor progression. Various epithelial-mesenchymal transition (EMT) responses have been reported and no common, EMT-defining gene expression program has been identified. Here, we have performed a comparative analysis of the EMT response, leveraging highly multiplexed single-cell RNA sequencing (scRNA-seq) to measure expression profiles of 103,999 cells from 960 samples, comprising 12 EMT time course experiments and independent kinase inhibitor screens for each. We demonstrate that the EMT is vastly context specific, with an average of only 22% of response genes being shared between any two conditions, and over half of all response genes were restricted to 1-2 time course experiments. Further, kinase inhibitor screens revealed signaling dependencies and modularity of these responses. These findings suggest that the EMT is not simply a single, linear process, but is highly variable and modular, warranting quantitative frameworks for understanding nuances of the transition.Epithelial-mesenchymal plasticity contributes to many biological processes, including tumor progression. Various epithelial-mesenchymal transition (EMT) responses have been reported and no common, EMT-defining gene expression program has been identified. Here, we have performed a comparative analysis of the EMT response, leveraging highly multiplexed single-cell RNA sequencing (scRNA-seq) to measure expression profiles of 103,999 cells from 960 samples, comprising 12 EMT time course experiments and independent kinase inhibitor screens for each. We demonstrate that the EMT is vastly context specific, with an average of only 22% of response genes being shared between any two conditions, and over half of all response genes were restricted to 1-2 time course experiments. Further, kinase inhibitor screens revealed signaling dependencies and modularity of these responses. These findings suggest that the EMT is not simply a single, linear process, but is highly variable and modular, warranting quantitative frameworks for understanding nuances of the transition. Epithelial–mesenchymal plasticity contributes to many biological processes, including tumor progression. Various epithelial–mesenchymal transition (EMT) responses have been reported and no common, EMT-defining gene expression program has been identified. Here, we have performed a comparative analysis of the EMT response, leveraging highly multiplexed single-cell RNA sequencing (scRNA-seq) to measure expression profiles of 103,999 cells from 960 samples, comprising 12 EMT time course experiments and independent kinase inhibitor screens for each. We demonstrate that the EMT is vastly context specific, with an average of only 22% of response genes being shared between any two conditions, and over half of all response genes were restricted to 1–2 time course experiments. Further, kinase inhibitor screens revealed signaling dependencies and modularity of these responses. These findings suggest that the EMT is not simply a single, linear process, but is highly variable and modular, warranting quantitative frameworks for understanding nuances of the transition. It is unclear if a common EMT expression program exists. Here, the authors perform multiplexed single-cell RNA sequencing across 12 EMT time courses and 16 kinase inhibitor screens, and find that EMT transcriptional responses are context specific and EMT is not a single, linear transition. Epithelial–mesenchymal plasticity contributes to many biological processes, including tumor progression. Various epithelial–mesenchymal transition (EMT) responses have been reported and no common, EMT-defining gene expression program has been identified. Here, we have performed a comparative analysis of the EMT response, leveraging highly multiplexed single-cell RNA sequencing (scRNA-seq) to measure expression profiles of 103,999 cells from 960 samples, comprising 12 EMT time course experiments and independent kinase inhibitor screens for each. We demonstrate that the EMT is vastly context specific, with an average of only 22% of response genes being shared between any two conditions, and over half of all response genes were restricted to 1–2 time course experiments. Further, kinase inhibitor screens revealed signaling dependencies and modularity of these responses. These findings suggest that the EMT is not simply a single, linear process, but is highly variable and modular, warranting quantitative frameworks for understanding nuances of the transition. It is unclear if a common EMT expression program exists. Here, the authors perform multiplexed single-cell RNA sequencing across 12 EMT time courses and 16 kinase inhibitor screens, and find that EMT transcriptional responses are context specific and EMT is not a single, linear transition. Epithelial–mesenchymal plasticity contributes to many biological processes, including tumor progression. Various epithelial–mesenchymal transition (EMT) responses have been reported and no common, EMT-defining gene expression program has been identified. Here, we have performed a comparative analysis of the EMT response, leveraging highly multiplexed single-cell RNA sequencing (scRNA-seq) to measure expression profiles of 103,999 cells from 960 samples, comprising 12 EMT time course experiments and independent kinase inhibitor screens for each. We demonstrate that the EMT is vastly context specific, with an average of only 22% of response genes being shared between any two conditions, and over half of all response genes were restricted to 1–2 time course experiments. Further, kinase inhibitor screens revealed signaling dependencies and modularity of these responses. These findings suggest that the EMT is not simply a single, linear process, but is highly variable and modular, warranting quantitative frameworks for understanding nuances of the transition. It is unclear if a common EMT expression program exists. Here, the authors perform multiplexed single-cell RNA sequencing across 12 EMT time courses and 16 kinase inhibitor screens, and find that EMT transcriptional responses are context specific and EMT is not a single, linear transition. |
| ArticleNumber | 2142 |
| Author | Cook, David P. Vanderhyden, Barbara C. |
| Author_xml | – sequence: 1 givenname: David P. orcidid: 0000-0001-7639-6724 surname: Cook fullname: Cook, David P. email: david.cook@uottawa.ca organization: Cancer Therapeutics Program, Ottawa Hospital Research Institute, Department of Cellular and Molecular Medicine, University of Ottawa – sequence: 2 givenname: Barbara C. orcidid: 0000-0002-7644-7189 surname: Vanderhyden fullname: Vanderhyden, Barbara C. email: bvanderhyden@ohri.ca organization: Cancer Therapeutics Program, Ottawa Hospital Research Institute, Department of Cellular and Molecular Medicine, University of Ottawa |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32358524$$D View this record in MEDLINE/PubMed |
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| PublicationTitle | Nature communications |
| PublicationTitleAbbrev | Nat Commun |
| PublicationTitleAlternate | Nat Commun |
| PublicationYear | 2020 |
| Publisher | Nature Publishing Group UK Nature Publishing Group Nature Portfolio |
| Publisher_xml | – name: Nature Publishing Group UK – name: Nature Publishing Group – name: Nature Portfolio |
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| Snippet | Epithelial–mesenchymal plasticity contributes to many biological processes, including tumor progression. Various epithelial–mesenchymal transition (EMT)... Epithelial-mesenchymal plasticity contributes to many biological processes, including tumor progression. Various epithelial-mesenchymal transition (EMT)... It is unclear if a common EMT expression program exists. Here, the authors perform multiplexed single-cell RNA sequencing across 12 EMT time courses and 16... |
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| SubjectTerms | 38 38/91 45 45/47 49 49/39 631/114/2163 631/67/2329 631/67/322 A549 Cells Biological activity Comparative analysis Context Enzyme inhibitors Epithelial Cells - metabolism Epithelial-Mesenchymal Transition - genetics Epithelial-Mesenchymal Transition - physiology Gene expression Gene Expression Regulation, Neoplastic - genetics Gene Expression Regulation, Neoplastic - physiology Gene sequencing Genes Humanities and Social Sciences Humans Kinases MCF-7 Cells Mesenchyme Modularity multidisciplinary Multiplexing Ribonucleic acid RNA Science Science (multidisciplinary) Sequence Analysis, RNA Signal Transduction - genetics Signal Transduction - physiology Transcription |
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| Title | Context specificity of the EMT transcriptional response |
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