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Altered transcriptional and chromatin responses to rhinovirus in bronchial epithelial cells from adults with asthma

There is a life-long relationship between rhinovirus (RV) infection and the development and clinical manifestations of asthma. In this study we demonstrate that cultured primary bronchial epithelial cells from adults with asthma (n = 9) show different transcriptional and chromatin responses to RV in...

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Autores principales: Helling, Britney A., Sobreira, Débora R., Hansen, Grace T., Sakabe, Noboru J., Luo, Kaixuan, Billstrand, Christine, Laxman, Bharathi, Nicolae, Raluca I., Nicolae, Dan L., Bochkov, Yury A., Gern, James E., Nobrega, Marcelo A., White, Steven R., Ober, Carole
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666152/
https://www.ncbi.nlm.nih.gov/pubmed/33188283
http://dx.doi.org/10.1038/s42003-020-01411-4
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author Helling, Britney A.
Sobreira, Débora R.
Hansen, Grace T.
Sakabe, Noboru J.
Luo, Kaixuan
Billstrand, Christine
Laxman, Bharathi
Nicolae, Raluca I.
Nicolae, Dan L.
Bochkov, Yury A.
Gern, James E.
Nobrega, Marcelo A.
White, Steven R.
Ober, Carole
author_facet Helling, Britney A.
Sobreira, Débora R.
Hansen, Grace T.
Sakabe, Noboru J.
Luo, Kaixuan
Billstrand, Christine
Laxman, Bharathi
Nicolae, Raluca I.
Nicolae, Dan L.
Bochkov, Yury A.
Gern, James E.
Nobrega, Marcelo A.
White, Steven R.
Ober, Carole
author_sort Helling, Britney A.
collection PubMed
description There is a life-long relationship between rhinovirus (RV) infection and the development and clinical manifestations of asthma. In this study we demonstrate that cultured primary bronchial epithelial cells from adults with asthma (n = 9) show different transcriptional and chromatin responses to RV infection compared to those without asthma (n = 9). Both the number and magnitude of transcriptional and chromatin responses to RV were muted in cells from asthma cases compared to controls. Pathway analysis of the transcriptionally responsive genes revealed enrichments of apoptotic pathways in controls but inflammatory pathways in asthma cases. Using promoter capture Hi-C we tethered regions of RV-responsive chromatin to RV-responsive genes and showed enrichment of these regions and genes at asthma GWAS loci. Taken together, our studies indicate a delayed or prolonged inflammatory state in cells from asthma cases and highlight genes that may contribute to genetic risk for asthma.
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spelling pubmed-76661522020-11-17 Altered transcriptional and chromatin responses to rhinovirus in bronchial epithelial cells from adults with asthma Helling, Britney A. Sobreira, Débora R. Hansen, Grace T. Sakabe, Noboru J. Luo, Kaixuan Billstrand, Christine Laxman, Bharathi Nicolae, Raluca I. Nicolae, Dan L. Bochkov, Yury A. Gern, James E. Nobrega, Marcelo A. White, Steven R. Ober, Carole Commun Biol Article There is a life-long relationship between rhinovirus (RV) infection and the development and clinical manifestations of asthma. In this study we demonstrate that cultured primary bronchial epithelial cells from adults with asthma (n = 9) show different transcriptional and chromatin responses to RV infection compared to those without asthma (n = 9). Both the number and magnitude of transcriptional and chromatin responses to RV were muted in cells from asthma cases compared to controls. Pathway analysis of the transcriptionally responsive genes revealed enrichments of apoptotic pathways in controls but inflammatory pathways in asthma cases. Using promoter capture Hi-C we tethered regions of RV-responsive chromatin to RV-responsive genes and showed enrichment of these regions and genes at asthma GWAS loci. Taken together, our studies indicate a delayed or prolonged inflammatory state in cells from asthma cases and highlight genes that may contribute to genetic risk for asthma. Nature Publishing Group UK 2020-11-13 /pmc/articles/PMC7666152/ /pubmed/33188283 http://dx.doi.org/10.1038/s42003-020-01411-4 Text en © The Author(s) 2020 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
Helling, Britney A.
Sobreira, Débora R.
Hansen, Grace T.
Sakabe, Noboru J.
Luo, Kaixuan
Billstrand, Christine
Laxman, Bharathi
Nicolae, Raluca I.
Nicolae, Dan L.
Bochkov, Yury A.
Gern, James E.
Nobrega, Marcelo A.
White, Steven R.
Ober, Carole
Altered transcriptional and chromatin responses to rhinovirus in bronchial epithelial cells from adults with asthma
title Altered transcriptional and chromatin responses to rhinovirus in bronchial epithelial cells from adults with asthma
title_full Altered transcriptional and chromatin responses to rhinovirus in bronchial epithelial cells from adults with asthma
title_fullStr Altered transcriptional and chromatin responses to rhinovirus in bronchial epithelial cells from adults with asthma
title_full_unstemmed Altered transcriptional and chromatin responses to rhinovirus in bronchial epithelial cells from adults with asthma
title_short Altered transcriptional and chromatin responses to rhinovirus in bronchial epithelial cells from adults with asthma
title_sort altered transcriptional and chromatin responses to rhinovirus in bronchial epithelial cells from adults with asthma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666152/
https://www.ncbi.nlm.nih.gov/pubmed/33188283
http://dx.doi.org/10.1038/s42003-020-01411-4
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