Single-Cell RNA Sequencing Analysis of the Heterogeneity in Gene Regulatory Networks in Colorectal Cancer

Colorectal cancer (CRC) manifests as gastrointestinal tumors with high intratumoral heterogeneity. Recent studies have demonstrated that CRC may consist of tumor cells with different consensus molecular subtypes (CMS). The advancements in single-cell RNA sequencing have facilitated the development o...

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Autores principales:	Rui-Qi Wang, Wei Zhao, Hai-Kui Yang, Jia-Mei Dong, Wei-Jie Lin, Fa-Zhong He, Min Cui, Zhi-Ling Zhou
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	colorectal cancer single-cell RNA sequencing consensus molecular subtypes gene regulation networks ERG Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/c3fee79df1a54903a73211536d0a71db
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spelling	oai:doaj.org-article:c3fee79df1a54903a73211536d0a71db2021-12-01T18:35:16ZSingle-Cell RNA Sequencing Analysis of the Heterogeneity in Gene Regulatory Networks in Colorectal Cancer2296-634X10.3389/fcell.2021.765578https://doaj.org/article/c3fee79df1a54903a73211536d0a71db2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.765578/fullhttps://doaj.org/toc/2296-634XColorectal cancer (CRC) manifests as gastrointestinal tumors with high intratumoral heterogeneity. Recent studies have demonstrated that CRC may consist of tumor cells with different consensus molecular subtypes (CMS). The advancements in single-cell RNA sequencing have facilitated the development of gene regulatory networks to decode key regulators for specific cell types. Herein, we comprehensively analyzed the CMS of CRC patients by using single-cell RNA-sequencing data. CMS for all malignant cells were assigned using CMScaller. Gene set variation analysis showed pathway activity differences consistent with those reported in previous studies. Cell–cell communication analysis confirmed that CMS1 was more closely related to immune cells, and that monocytes and macrophages play dominant roles in the CRC tumor microenvironment. On the basis of the constructed gene regulation networks (GRNs) for each subtype, we identified that the critical transcription factor ERG is universally activated and upregulated in all CMS in comparison with normal cells, and that it performed diverse roles by regulating the expression of different downstream genes. In summary, molecular subtyping of single-cell RNA-sequencing data for colorectal cancer could elucidate the heterogeneity in gene regulatory networks and identify critical regulators of CRC.Rui-Qi WangWei ZhaoHai-Kui YangJia-Mei DongWei-Jie LinFa-Zhong HeMin CuiZhi-Ling ZhouFrontiers Media S.A.articlecolorectal cancersingle-cell RNA sequencingconsensus molecular subtypesgene regulation networksERGBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	colorectal cancer single-cell RNA sequencing consensus molecular subtypes gene regulation networks ERG Biology (General) QH301-705.5
spellingShingle	colorectal cancer single-cell RNA sequencing consensus molecular subtypes gene regulation networks ERG Biology (General) QH301-705.5 Rui-Qi Wang Wei Zhao Hai-Kui Yang Jia-Mei Dong Wei-Jie Lin Fa-Zhong He Min Cui Zhi-Ling Zhou Single-Cell RNA Sequencing Analysis of the Heterogeneity in Gene Regulatory Networks in Colorectal Cancer
description	Colorectal cancer (CRC) manifests as gastrointestinal tumors with high intratumoral heterogeneity. Recent studies have demonstrated that CRC may consist of tumor cells with different consensus molecular subtypes (CMS). The advancements in single-cell RNA sequencing have facilitated the development of gene regulatory networks to decode key regulators for specific cell types. Herein, we comprehensively analyzed the CMS of CRC patients by using single-cell RNA-sequencing data. CMS for all malignant cells were assigned using CMScaller. Gene set variation analysis showed pathway activity differences consistent with those reported in previous studies. Cell–cell communication analysis confirmed that CMS1 was more closely related to immune cells, and that monocytes and macrophages play dominant roles in the CRC tumor microenvironment. On the basis of the constructed gene regulation networks (GRNs) for each subtype, we identified that the critical transcription factor ERG is universally activated and upregulated in all CMS in comparison with normal cells, and that it performed diverse roles by regulating the expression of different downstream genes. In summary, molecular subtyping of single-cell RNA-sequencing data for colorectal cancer could elucidate the heterogeneity in gene regulatory networks and identify critical regulators of CRC.
format	article
author	Rui-Qi Wang Wei Zhao Hai-Kui Yang Jia-Mei Dong Wei-Jie Lin Fa-Zhong He Min Cui Zhi-Ling Zhou
author_facet	Rui-Qi Wang Wei Zhao Hai-Kui Yang Jia-Mei Dong Wei-Jie Lin Fa-Zhong He Min Cui Zhi-Ling Zhou
author_sort	Rui-Qi Wang
title	Single-Cell RNA Sequencing Analysis of the Heterogeneity in Gene Regulatory Networks in Colorectal Cancer
title_short	Single-Cell RNA Sequencing Analysis of the Heterogeneity in Gene Regulatory Networks in Colorectal Cancer
title_full	Single-Cell RNA Sequencing Analysis of the Heterogeneity in Gene Regulatory Networks in Colorectal Cancer
title_fullStr	Single-Cell RNA Sequencing Analysis of the Heterogeneity in Gene Regulatory Networks in Colorectal Cancer
title_full_unstemmed	Single-Cell RNA Sequencing Analysis of the Heterogeneity in Gene Regulatory Networks in Colorectal Cancer
title_sort	single-cell rna sequencing analysis of the heterogeneity in gene regulatory networks in colorectal cancer
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/c3fee79df1a54903a73211536d0a71db
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Single-Cell RNA Sequencing Analysis of the Heterogeneity in Gene Regulatory Networks in Colorectal Cancer

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