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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...
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/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. |
format | Online Article Text |
id | pubmed-8669944 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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