Cargando…

Cell Type-Specific Induction of Inflammation-Associated Genes in Crohn’s Disease and Colorectal Cancer

Based on the rapid increase in incidence of inflammatory bowel disease (IBD), the identification of susceptibility genes and cell populations contributing to this condition is essential. Previous studies suggested multiple genes associated with the susceptibility of IBD; however, due to the analysis...

Descripción completa

Detalles Bibliográficos
Autores principales: Saul, Dominik, Leite Barros, Luísa, Wixom, Alexander Q., Gellhaus, Benjamin, Gibbons, Hunter R., Faubion, William A., Kosinsky, Robyn Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955412/
https://www.ncbi.nlm.nih.gov/pubmed/35328501
http://dx.doi.org/10.3390/ijms23063082
_version_ 1784676329983049728
author Saul, Dominik
Leite Barros, Luísa
Wixom, Alexander Q.
Gellhaus, Benjamin
Gibbons, Hunter R.
Faubion, William A.
Kosinsky, Robyn Laura
author_facet Saul, Dominik
Leite Barros, Luísa
Wixom, Alexander Q.
Gellhaus, Benjamin
Gibbons, Hunter R.
Faubion, William A.
Kosinsky, Robyn Laura
author_sort Saul, Dominik
collection PubMed
description Based on the rapid increase in incidence of inflammatory bowel disease (IBD), the identification of susceptibility genes and cell populations contributing to this condition is essential. Previous studies suggested multiple genes associated with the susceptibility of IBD; however, due to the analysis of whole-tissue samples, the contribution of individual cell populations remains widely unresolved. Single-cell RNA sequencing (scRNA-seq) provides the opportunity to identify underlying cellular populations. We determined the enrichment of Crohn’s disease (CD)-induced genes in a publicly available Crohn’s disease scRNA-seq dataset and detected the strongest induction of these genes in innate lymphoid cells (ILC1), highly activated T cells and dendritic cells, pericytes and activated fibroblasts, as well as epithelial cells. Notably, these genes were highly enriched in IBD-associated neoplasia, as well as sporadic colorectal cancer (CRC). Indeed, the same six cell populations displayed an upregulation of CD-induced genes in a CRC scRNA-seq dataset. Finally, after integrating and harmonizing the CD and CRC scRNA-seq data, we demonstrated that these six cell types display a gradual increase in gene expression levels from a healthy state to an inflammatory and tumorous state. Together, we identified cell populations that specifically upregulate CD-induced genes in CD and CRC patients and could, therefore, contribute to inflammation-associated tumor development.
format Online
Article
Text
id pubmed-8955412
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-89554122022-03-26 Cell Type-Specific Induction of Inflammation-Associated Genes in Crohn’s Disease and Colorectal Cancer Saul, Dominik Leite Barros, Luísa Wixom, Alexander Q. Gellhaus, Benjamin Gibbons, Hunter R. Faubion, William A. Kosinsky, Robyn Laura Int J Mol Sci Article Based on the rapid increase in incidence of inflammatory bowel disease (IBD), the identification of susceptibility genes and cell populations contributing to this condition is essential. Previous studies suggested multiple genes associated with the susceptibility of IBD; however, due to the analysis of whole-tissue samples, the contribution of individual cell populations remains widely unresolved. Single-cell RNA sequencing (scRNA-seq) provides the opportunity to identify underlying cellular populations. We determined the enrichment of Crohn’s disease (CD)-induced genes in a publicly available Crohn’s disease scRNA-seq dataset and detected the strongest induction of these genes in innate lymphoid cells (ILC1), highly activated T cells and dendritic cells, pericytes and activated fibroblasts, as well as epithelial cells. Notably, these genes were highly enriched in IBD-associated neoplasia, as well as sporadic colorectal cancer (CRC). Indeed, the same six cell populations displayed an upregulation of CD-induced genes in a CRC scRNA-seq dataset. Finally, after integrating and harmonizing the CD and CRC scRNA-seq data, we demonstrated that these six cell types display a gradual increase in gene expression levels from a healthy state to an inflammatory and tumorous state. Together, we identified cell populations that specifically upregulate CD-induced genes in CD and CRC patients and could, therefore, contribute to inflammation-associated tumor development. MDPI 2022-03-12 /pmc/articles/PMC8955412/ /pubmed/35328501 http://dx.doi.org/10.3390/ijms23063082 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Saul, Dominik
Leite Barros, Luísa
Wixom, Alexander Q.
Gellhaus, Benjamin
Gibbons, Hunter R.
Faubion, William A.
Kosinsky, Robyn Laura
Cell Type-Specific Induction of Inflammation-Associated Genes in Crohn’s Disease and Colorectal Cancer
title Cell Type-Specific Induction of Inflammation-Associated Genes in Crohn’s Disease and Colorectal Cancer
title_full Cell Type-Specific Induction of Inflammation-Associated Genes in Crohn’s Disease and Colorectal Cancer
title_fullStr Cell Type-Specific Induction of Inflammation-Associated Genes in Crohn’s Disease and Colorectal Cancer
title_full_unstemmed Cell Type-Specific Induction of Inflammation-Associated Genes in Crohn’s Disease and Colorectal Cancer
title_short Cell Type-Specific Induction of Inflammation-Associated Genes in Crohn’s Disease and Colorectal Cancer
title_sort cell type-specific induction of inflammation-associated genes in crohn’s disease and colorectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955412/
https://www.ncbi.nlm.nih.gov/pubmed/35328501
http://dx.doi.org/10.3390/ijms23063082
work_keys_str_mv AT sauldominik celltypespecificinductionofinflammationassociatedgenesincrohnsdiseaseandcolorectalcancer
AT leitebarrosluisa celltypespecificinductionofinflammationassociatedgenesincrohnsdiseaseandcolorectalcancer
AT wixomalexanderq celltypespecificinductionofinflammationassociatedgenesincrohnsdiseaseandcolorectalcancer
AT gellhausbenjamin celltypespecificinductionofinflammationassociatedgenesincrohnsdiseaseandcolorectalcancer
AT gibbonshunterr celltypespecificinductionofinflammationassociatedgenesincrohnsdiseaseandcolorectalcancer
AT faubionwilliama celltypespecificinductionofinflammationassociatedgenesincrohnsdiseaseandcolorectalcancer
AT kosinskyrobynlaura celltypespecificinductionofinflammationassociatedgenesincrohnsdiseaseandcolorectalcancer