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Inference of Intercellular Communications and Multilayer Gene-Regulations of Epithelial–Mesenchymal Transition From Single-Cell Transcriptomic Data
Epithelial-to-mesenchymal transition (EMT) plays an important role in many biological processes during development and cancer. The advent of single-cell transcriptome sequencing techniques allows the dissection of dynamical details underlying EMT with unprecedented resolution. Despite several single...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820899/ https://www.ncbi.nlm.nih.gov/pubmed/33488673 http://dx.doi.org/10.3389/fgene.2020.604585 |
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author | Sha, Yutong Wang, Shuxiong Bocci, Federico Zhou, Peijie Nie, Qing |
author_facet | Sha, Yutong Wang, Shuxiong Bocci, Federico Zhou, Peijie Nie, Qing |
author_sort | Sha, Yutong |
collection | PubMed |
description | Epithelial-to-mesenchymal transition (EMT) plays an important role in many biological processes during development and cancer. The advent of single-cell transcriptome sequencing techniques allows the dissection of dynamical details underlying EMT with unprecedented resolution. Despite several single-cell data analysis on EMT, how cell communicates and regulates dynamics along the EMT trajectory remains elusive. Using single-cell transcriptomic datasets, here we infer the cell–cell communications and the multilayer gene–gene regulation networks to analyze and visualize the complex cellular crosstalk and the underlying gene regulatory dynamics along EMT. Combining with trajectory analysis, our approach reveals the existence of multiple intermediate cell states (ICSs) with hybrid epithelial and mesenchymal features. Analyses on the time-series datasets from cancer cell lines with different inducing factors show that the induced EMTs are context-specific: the EMT induced by transforming growth factor B1 (TGFB1) is synchronous, whereas the EMTs induced by epidermal growth factor and tumor necrosis factor are asynchronous, and the responses of TGF-β pathway in terms of gene expression regulations are heterogeneous under different treatments or among various cell states. Meanwhile, network topology analysis suggests that the ICSs during EMT serve as the signaling in cellular communication under different conditions. Interestingly, our analysis of a mouse skin squamous cell carcinoma dataset also suggests regardless of the significant discrepancy in concrete genes between in vitro and in vivo EMT systems, the ICSs play dominant role in the TGF-β signaling crosstalk. Overall, our approach reveals the multiscale mechanisms coupling cell–cell communications and gene–gene regulations responsible for complex cell-state transitions. |
format | Online Article Text |
id | pubmed-7820899 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78208992021-01-23 Inference of Intercellular Communications and Multilayer Gene-Regulations of Epithelial–Mesenchymal Transition From Single-Cell Transcriptomic Data Sha, Yutong Wang, Shuxiong Bocci, Federico Zhou, Peijie Nie, Qing Front Genet Genetics Epithelial-to-mesenchymal transition (EMT) plays an important role in many biological processes during development and cancer. The advent of single-cell transcriptome sequencing techniques allows the dissection of dynamical details underlying EMT with unprecedented resolution. Despite several single-cell data analysis on EMT, how cell communicates and regulates dynamics along the EMT trajectory remains elusive. Using single-cell transcriptomic datasets, here we infer the cell–cell communications and the multilayer gene–gene regulation networks to analyze and visualize the complex cellular crosstalk and the underlying gene regulatory dynamics along EMT. Combining with trajectory analysis, our approach reveals the existence of multiple intermediate cell states (ICSs) with hybrid epithelial and mesenchymal features. Analyses on the time-series datasets from cancer cell lines with different inducing factors show that the induced EMTs are context-specific: the EMT induced by transforming growth factor B1 (TGFB1) is synchronous, whereas the EMTs induced by epidermal growth factor and tumor necrosis factor are asynchronous, and the responses of TGF-β pathway in terms of gene expression regulations are heterogeneous under different treatments or among various cell states. Meanwhile, network topology analysis suggests that the ICSs during EMT serve as the signaling in cellular communication under different conditions. Interestingly, our analysis of a mouse skin squamous cell carcinoma dataset also suggests regardless of the significant discrepancy in concrete genes between in vitro and in vivo EMT systems, the ICSs play dominant role in the TGF-β signaling crosstalk. Overall, our approach reveals the multiscale mechanisms coupling cell–cell communications and gene–gene regulations responsible for complex cell-state transitions. Frontiers Media S.A. 2021-01-08 /pmc/articles/PMC7820899/ /pubmed/33488673 http://dx.doi.org/10.3389/fgene.2020.604585 Text en Copyright © 2021 Sha, Wang, Bocci, Zhou and Nie. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Sha, Yutong Wang, Shuxiong Bocci, Federico Zhou, Peijie Nie, Qing Inference of Intercellular Communications and Multilayer Gene-Regulations of Epithelial–Mesenchymal Transition From Single-Cell Transcriptomic Data |
title | Inference of Intercellular Communications and Multilayer Gene-Regulations of Epithelial–Mesenchymal Transition From Single-Cell Transcriptomic Data |
title_full | Inference of Intercellular Communications and Multilayer Gene-Regulations of Epithelial–Mesenchymal Transition From Single-Cell Transcriptomic Data |
title_fullStr | Inference of Intercellular Communications and Multilayer Gene-Regulations of Epithelial–Mesenchymal Transition From Single-Cell Transcriptomic Data |
title_full_unstemmed | Inference of Intercellular Communications and Multilayer Gene-Regulations of Epithelial–Mesenchymal Transition From Single-Cell Transcriptomic Data |
title_short | Inference of Intercellular Communications and Multilayer Gene-Regulations of Epithelial–Mesenchymal Transition From Single-Cell Transcriptomic Data |
title_sort | inference of intercellular communications and multilayer gene-regulations of epithelial–mesenchymal transition from single-cell transcriptomic data |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820899/ https://www.ncbi.nlm.nih.gov/pubmed/33488673 http://dx.doi.org/10.3389/fgene.2020.604585 |
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