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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: Wang, Rui-Qi, Zhao, Wei, Yang, Hai-Kui, Dong, Jia-Mei, Lin, Wei-Jie, He, Fa-Zhong, Cui, Min, Zhou, Zhi-Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8669944/
https://www.ncbi.nlm.nih.gov/pubmed/34917613
http://dx.doi.org/10.3389/fcell.2021.765578
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author Wang, Rui-Qi
Zhao, Wei
Yang, Hai-Kui
Dong, Jia-Mei
Lin, Wei-Jie
He, Fa-Zhong
Cui, Min
Zhou, Zhi-Ling
author_facet Wang, Rui-Qi
Zhao, Wei
Yang, Hai-Kui
Dong, Jia-Mei
Lin, Wei-Jie
He, Fa-Zhong
Cui, Min
Zhou, Zhi-Ling
author_sort Wang, Rui-Qi
collection PubMed
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.
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spelling pubmed-86699442021-12-15 Single-Cell RNA Sequencing Analysis of the Heterogeneity in Gene Regulatory Networks in Colorectal Cancer Wang, Rui-Qi Zhao, Wei Yang, Hai-Kui Dong, Jia-Mei Lin, Wei-Jie He, Fa-Zhong Cui, Min Zhou, Zhi-Ling Front Cell Dev Biol Cell and Developmental Biology 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. Frontiers Media S.A. 2021-11-30 /pmc/articles/PMC8669944/ /pubmed/34917613 http://dx.doi.org/10.3389/fcell.2021.765578 Text en Copyright © 2021 Wang, Zhao, Yang, Dong, Lin, He, Cui and Zhou. https://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 Cell and Developmental Biology
Wang, Rui-Qi
Zhao, Wei
Yang, Hai-Kui
Dong, Jia-Mei
Lin, Wei-Jie
He, Fa-Zhong
Cui, Min
Zhou, Zhi-Ling
Single-Cell RNA Sequencing Analysis of the Heterogeneity in Gene Regulatory Networks in Colorectal Cancer
title 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_short 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
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8669944/
https://www.ncbi.nlm.nih.gov/pubmed/34917613
http://dx.doi.org/10.3389/fcell.2021.765578
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