Single-Cell RNA-Seq Analysis Reveals the Acquisition of Cancer Stem Cell Traits and Increase of Cell–Cell Signaling during EMT Progression

Intermediate cell states (ICSs) during the epithelial–mesenchymal transition (EMT) are emerging as a driving force of cancer invasion and metastasis. ICSs typically exhibit hybrid epithelial/mesenchymal characteristics as well as cancer stem cell (CSC) traits including proliferation and drug resista...

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Autores principales: Federico Bocci, Peijie Zhou, Qing Nie
Formato: article
Lenguaje:EN
Publicado: MDPI AG 2021
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EMT
Acceso en línea:https://doaj.org/article/c7fc6915883b4b429d859f6f56a7b82b
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spelling oai:doaj.org-article:c7fc6915883b4b429d859f6f56a7b82b2021-11-25T17:03:32ZSingle-Cell RNA-Seq Analysis Reveals the Acquisition of Cancer Stem Cell Traits and Increase of Cell–Cell Signaling during EMT Progression10.3390/cancers132257262072-6694https://doaj.org/article/c7fc6915883b4b429d859f6f56a7b82b2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5726https://doaj.org/toc/2072-6694Intermediate cell states (ICSs) during the epithelial–mesenchymal transition (EMT) are emerging as a driving force of cancer invasion and metastasis. ICSs typically exhibit hybrid epithelial/mesenchymal characteristics as well as cancer stem cell (CSC) traits including proliferation and drug resistance. Here, we analyze several single-cell RNA-seq (scRNA-seq) datasets to investigate the relation between several axes of cancer progression including EMT, CSC traits, and cell–cell signaling. To accomplish this task, we integrate computational methods for clustering and trajectory inference with analysis of EMT gene signatures, CSC markers, and cell–cell signaling pathways, and highlight conserved and specific processes across the datasets. Our analysis reveals that “standard” measures of pluripotency often used in developmental contexts do not necessarily correlate with EMT progression and expression of CSC-related markers. Conversely, an EMT circuit energy that quantifies the co-expression of epithelial and mesenchymal genes consistently increases along EMT trajectories across different cancer types and anatomical locations. Moreover, despite the high context specificity of signal transduction across different cell types, cells undergoing EMT always increased their potential to send and receive signals from other cells.Federico BocciPeijie ZhouQing NieMDPI AGarticleEMTcancer stem cellscell–cell signalingscRNA-seqepithelial–mesenchymal plasticityhybrid E/MNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5726, p 5726 (2021)
institution DOAJ
collection DOAJ
language EN
topic EMT
cancer stem cells
cell–cell signaling
scRNA-seq
epithelial–mesenchymal plasticity
hybrid E/M
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle EMT
cancer stem cells
cell–cell signaling
scRNA-seq
epithelial–mesenchymal plasticity
hybrid E/M
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Federico Bocci
Peijie Zhou
Qing Nie
Single-Cell RNA-Seq Analysis Reveals the Acquisition of Cancer Stem Cell Traits and Increase of Cell–Cell Signaling during EMT Progression
description Intermediate cell states (ICSs) during the epithelial–mesenchymal transition (EMT) are emerging as a driving force of cancer invasion and metastasis. ICSs typically exhibit hybrid epithelial/mesenchymal characteristics as well as cancer stem cell (CSC) traits including proliferation and drug resistance. Here, we analyze several single-cell RNA-seq (scRNA-seq) datasets to investigate the relation between several axes of cancer progression including EMT, CSC traits, and cell–cell signaling. To accomplish this task, we integrate computational methods for clustering and trajectory inference with analysis of EMT gene signatures, CSC markers, and cell–cell signaling pathways, and highlight conserved and specific processes across the datasets. Our analysis reveals that “standard” measures of pluripotency often used in developmental contexts do not necessarily correlate with EMT progression and expression of CSC-related markers. Conversely, an EMT circuit energy that quantifies the co-expression of epithelial and mesenchymal genes consistently increases along EMT trajectories across different cancer types and anatomical locations. Moreover, despite the high context specificity of signal transduction across different cell types, cells undergoing EMT always increased their potential to send and receive signals from other cells.
format article
author Federico Bocci
Peijie Zhou
Qing Nie
author_facet Federico Bocci
Peijie Zhou
Qing Nie
author_sort Federico Bocci
title Single-Cell RNA-Seq Analysis Reveals the Acquisition of Cancer Stem Cell Traits and Increase of Cell–Cell Signaling during EMT Progression
title_short Single-Cell RNA-Seq Analysis Reveals the Acquisition of Cancer Stem Cell Traits and Increase of Cell–Cell Signaling during EMT Progression
title_full Single-Cell RNA-Seq Analysis Reveals the Acquisition of Cancer Stem Cell Traits and Increase of Cell–Cell Signaling during EMT Progression
title_fullStr Single-Cell RNA-Seq Analysis Reveals the Acquisition of Cancer Stem Cell Traits and Increase of Cell–Cell Signaling during EMT Progression
title_full_unstemmed Single-Cell RNA-Seq Analysis Reveals the Acquisition of Cancer Stem Cell Traits and Increase of Cell–Cell Signaling during EMT Progression
title_sort single-cell rna-seq analysis reveals the acquisition of cancer stem cell traits and increase of cell–cell signaling during emt progression
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/c7fc6915883b4b429d859f6f56a7b82b
work_keys_str_mv AT federicobocci singlecellrnaseqanalysisrevealstheacquisitionofcancerstemcelltraitsandincreaseofcellcellsignalingduringemtprogression
AT peijiezhou singlecellrnaseqanalysisrevealstheacquisitionofcancerstemcelltraitsandincreaseofcellcellsignalingduringemtprogression
AT qingnie singlecellrnaseqanalysisrevealstheacquisitionofcancerstemcelltraitsandincreaseofcellcellsignalingduringemtprogression
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