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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Vydané v:Nature communications Ročník 11; číslo 1; s. 2142 - 9
Hlavní autori: Cook, David P., Vanderhyden, Barbara C.
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: London Nature Publishing Group UK 01.05.2020
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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
ISSN:2041-1723, 2041-1723
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Popis
Shrnutí: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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SourceType-Scholarly Journals-1
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-020-16066-2