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Downregulation of MALAT1 is a hallmark of tissue and peripheral proliferative T cells in COVID-19
T cells play key protective but also pathogenic roles in COVID-19. We studied the expression of long non-coding RNAs (lncRNAs) in COVID-19 T-cell transcriptomes by integrating previously published single-cell RNA sequencing datasets. The long intergenic non-coding RNA MALAT1 was the most highly tran...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10243916/ https://www.ncbi.nlm.nih.gov/pubmed/36869729 http://dx.doi.org/10.1093/cei/uxad034 |
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author | Dey, Shoumit Ashwin, Helen Milross, Luke Hunter, Bethany Majo, Joaquim Filby, Andrew J Fisher, Andrew J Kaye, Paul M Lagos, Dimitris |
author_facet | Dey, Shoumit Ashwin, Helen Milross, Luke Hunter, Bethany Majo, Joaquim Filby, Andrew J Fisher, Andrew J Kaye, Paul M Lagos, Dimitris |
author_sort | Dey, Shoumit |
collection | PubMed |
description | T cells play key protective but also pathogenic roles in COVID-19. We studied the expression of long non-coding RNAs (lncRNAs) in COVID-19 T-cell transcriptomes by integrating previously published single-cell RNA sequencing datasets. The long intergenic non-coding RNA MALAT1 was the most highly transcribed lncRNA in T cells, with Th1 cells demonstrating the lowest and CD8+ resident memory cells the highest MALAT1 expression, amongst CD4+ and CD8+ T-cells populations, respectively. We then identified gene signatures that covaried with MALAT1 in single T cells. A significantly higher number of transcripts correlated negatively with MALAT1 than those that correlated. Enriched functional annotations of the MALAT1- anti-correlating gene signature included processes associated with T-cell activation such as cell division, oxidative phosphorylation, and response to cytokine. The MALAT1 anti-correlating gene signature shared by both CD4+ and CD8+ T-cells marked dividing T cells in both the lung and blood of COVID-19 patients. Focussing on the tissue, we used an independent patient cohort of post-mortem COVID-19 lung samples and demonstrated that MALAT1 suppression was indeed a marker of MKI67+ proliferating CD8+ T cells. Our results reveal MALAT1 suppression and its associated gene signature are a hallmark of human proliferating T cells. |
format | Online Article Text |
id | pubmed-10243916 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-102439162023-06-07 Downregulation of MALAT1 is a hallmark of tissue and peripheral proliferative T cells in COVID-19 Dey, Shoumit Ashwin, Helen Milross, Luke Hunter, Bethany Majo, Joaquim Filby, Andrew J Fisher, Andrew J Kaye, Paul M Lagos, Dimitris Clin Exp Immunol Infection/Infectious Disease T cells play key protective but also pathogenic roles in COVID-19. We studied the expression of long non-coding RNAs (lncRNAs) in COVID-19 T-cell transcriptomes by integrating previously published single-cell RNA sequencing datasets. The long intergenic non-coding RNA MALAT1 was the most highly transcribed lncRNA in T cells, with Th1 cells demonstrating the lowest and CD8+ resident memory cells the highest MALAT1 expression, amongst CD4+ and CD8+ T-cells populations, respectively. We then identified gene signatures that covaried with MALAT1 in single T cells. A significantly higher number of transcripts correlated negatively with MALAT1 than those that correlated. Enriched functional annotations of the MALAT1- anti-correlating gene signature included processes associated with T-cell activation such as cell division, oxidative phosphorylation, and response to cytokine. The MALAT1 anti-correlating gene signature shared by both CD4+ and CD8+ T-cells marked dividing T cells in both the lung and blood of COVID-19 patients. Focussing on the tissue, we used an independent patient cohort of post-mortem COVID-19 lung samples and demonstrated that MALAT1 suppression was indeed a marker of MKI67+ proliferating CD8+ T cells. Our results reveal MALAT1 suppression and its associated gene signature are a hallmark of human proliferating T cells. Oxford University Press 2023-03-03 /pmc/articles/PMC10243916/ /pubmed/36869729 http://dx.doi.org/10.1093/cei/uxad034 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Infection/Infectious Disease Dey, Shoumit Ashwin, Helen Milross, Luke Hunter, Bethany Majo, Joaquim Filby, Andrew J Fisher, Andrew J Kaye, Paul M Lagos, Dimitris Downregulation of MALAT1 is a hallmark of tissue and peripheral proliferative T cells in COVID-19 |
title | Downregulation of MALAT1 is a hallmark of tissue and peripheral proliferative T cells in COVID-19 |
title_full | Downregulation of MALAT1 is a hallmark of tissue and peripheral proliferative T cells in COVID-19 |
title_fullStr | Downregulation of MALAT1 is a hallmark of tissue and peripheral proliferative T cells in COVID-19 |
title_full_unstemmed | Downregulation of MALAT1 is a hallmark of tissue and peripheral proliferative T cells in COVID-19 |
title_short | Downregulation of MALAT1 is a hallmark of tissue and peripheral proliferative T cells in COVID-19 |
title_sort | downregulation of malat1 is a hallmark of tissue and peripheral proliferative t cells in covid-19 |
topic | Infection/Infectious Disease |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10243916/ https://www.ncbi.nlm.nih.gov/pubmed/36869729 http://dx.doi.org/10.1093/cei/uxad034 |
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