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Cell type-specific gene expression patterns associated with posttraumatic stress disorder in World Trade Center responders

Posttraumatic stress disorder (PTSD), a chronic disorder resulting from severe trauma, has been linked to immunologic dysregulation. Gene expression profiling has emerged as a promising tool for understanding the pathophysiology of PTSD. However, to date, all but one gene expression study was based...

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Autores principales: Kuan, Pei-Fen, Yang, Xiaohua, Clouston, Sean, Ren, Xu, Kotov, Roman, Waszczuk, Monika, Singh, Prashant K., Glenn, Sean T., Gomez, Eduardo Cortes, Wang, Jianmin, Bromet, Evelyn, Luft, Benjamin J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341096/
https://www.ncbi.nlm.nih.gov/pubmed/30664621
http://dx.doi.org/10.1038/s41398-018-0355-8
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author Kuan, Pei-Fen
Yang, Xiaohua
Clouston, Sean
Ren, Xu
Kotov, Roman
Waszczuk, Monika
Singh, Prashant K.
Glenn, Sean T.
Gomez, Eduardo Cortes
Wang, Jianmin
Bromet, Evelyn
Luft, Benjamin J.
author_facet Kuan, Pei-Fen
Yang, Xiaohua
Clouston, Sean
Ren, Xu
Kotov, Roman
Waszczuk, Monika
Singh, Prashant K.
Glenn, Sean T.
Gomez, Eduardo Cortes
Wang, Jianmin
Bromet, Evelyn
Luft, Benjamin J.
author_sort Kuan, Pei-Fen
collection PubMed
description Posttraumatic stress disorder (PTSD), a chronic disorder resulting from severe trauma, has been linked to immunologic dysregulation. Gene expression profiling has emerged as a promising tool for understanding the pathophysiology of PTSD. However, to date, all but one gene expression study was based on whole blood or unsorted peripheral blood mononuclear cell (PBMC), a complex tissue consisting of several populations of cells. The objective of this study was to utilize RNA sequencing to simultaneously profile the gene expression of four immune cell subpopulations (CD4T, CD8T, B cells, and monocytes) in 39 World Trade Center responders (20 with and 19 without PTSD) to determine which immune subsets play a role in the transcriptomic changes found in whole blood. Transcriptome-wide analyses identified cell-specific and shared differentially expressed genes across the four cell types. FKBP5 and PI4KAP1 genes were consistently upregulated across all cell types. Notably, REST and SEPT4, genes linked to neurodegeneration, were among the top differentially expressed genes in monocytes. Pathway analyses identified differentially expressed gene sets involved in mast cell activation and regulation in CD4T, interferon-beta production in CD8T, and neutrophil-related gene sets in monocytes. These findings suggest that gene expression indicative of immune dysregulation is common across several immune cell populations in PTSD. Furthermore, given notable differences between cell subpopulations in gene expression associated with PTSD, the results also indicate that it may be valuable to analyze different cell populations separately. Monocytes may constitute a key cell type to target in research on gene expression profile of PTSD.
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spelling pubmed-63410962019-01-23 Cell type-specific gene expression patterns associated with posttraumatic stress disorder in World Trade Center responders Kuan, Pei-Fen Yang, Xiaohua Clouston, Sean Ren, Xu Kotov, Roman Waszczuk, Monika Singh, Prashant K. Glenn, Sean T. Gomez, Eduardo Cortes Wang, Jianmin Bromet, Evelyn Luft, Benjamin J. Transl Psychiatry Article Posttraumatic stress disorder (PTSD), a chronic disorder resulting from severe trauma, has been linked to immunologic dysregulation. Gene expression profiling has emerged as a promising tool for understanding the pathophysiology of PTSD. However, to date, all but one gene expression study was based on whole blood or unsorted peripheral blood mononuclear cell (PBMC), a complex tissue consisting of several populations of cells. The objective of this study was to utilize RNA sequencing to simultaneously profile the gene expression of four immune cell subpopulations (CD4T, CD8T, B cells, and monocytes) in 39 World Trade Center responders (20 with and 19 without PTSD) to determine which immune subsets play a role in the transcriptomic changes found in whole blood. Transcriptome-wide analyses identified cell-specific and shared differentially expressed genes across the four cell types. FKBP5 and PI4KAP1 genes were consistently upregulated across all cell types. Notably, REST and SEPT4, genes linked to neurodegeneration, were among the top differentially expressed genes in monocytes. Pathway analyses identified differentially expressed gene sets involved in mast cell activation and regulation in CD4T, interferon-beta production in CD8T, and neutrophil-related gene sets in monocytes. These findings suggest that gene expression indicative of immune dysregulation is common across several immune cell populations in PTSD. Furthermore, given notable differences between cell subpopulations in gene expression associated with PTSD, the results also indicate that it may be valuable to analyze different cell populations separately. Monocytes may constitute a key cell type to target in research on gene expression profile of PTSD. Nature Publishing Group UK 2019-01-15 /pmc/articles/PMC6341096/ /pubmed/30664621 http://dx.doi.org/10.1038/s41398-018-0355-8 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kuan, Pei-Fen
Yang, Xiaohua
Clouston, Sean
Ren, Xu
Kotov, Roman
Waszczuk, Monika
Singh, Prashant K.
Glenn, Sean T.
Gomez, Eduardo Cortes
Wang, Jianmin
Bromet, Evelyn
Luft, Benjamin J.
Cell type-specific gene expression patterns associated with posttraumatic stress disorder in World Trade Center responders
title Cell type-specific gene expression patterns associated with posttraumatic stress disorder in World Trade Center responders
title_full Cell type-specific gene expression patterns associated with posttraumatic stress disorder in World Trade Center responders
title_fullStr Cell type-specific gene expression patterns associated with posttraumatic stress disorder in World Trade Center responders
title_full_unstemmed Cell type-specific gene expression patterns associated with posttraumatic stress disorder in World Trade Center responders
title_short Cell type-specific gene expression patterns associated with posttraumatic stress disorder in World Trade Center responders
title_sort cell type-specific gene expression patterns associated with posttraumatic stress disorder in world trade center responders
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341096/
https://www.ncbi.nlm.nih.gov/pubmed/30664621
http://dx.doi.org/10.1038/s41398-018-0355-8
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