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Transcriptomic Remodelling of Fetal Endothelial Cells During Establishment of Inflammatory Memory
Inflammatory memory involves the molecular and cellular ‘reprogramming’ of innate immune cells following exogenous stimuli, leading to non-specific protection against subsequent pathogen exposure. This phenomenon has now also been described in non-hematopoietic cells, such as human fetal and adult e...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8640490/ https://www.ncbi.nlm.nih.gov/pubmed/34867995 http://dx.doi.org/10.3389/fimmu.2021.757393 |
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author | Weiss, Elisa Vlahos, Amanda Kim, Bowon Wijegunasekara, Sachintha Shanmuganathan, Dhanya Aitken, Thomas Joo, Ji-Hoon E. Imran, Samira Shepherd, Rebecca Craig, Jeffrey M. Green, Mark Hiden, Ursula Novakovic, Boris Saffery, Richard |
author_facet | Weiss, Elisa Vlahos, Amanda Kim, Bowon Wijegunasekara, Sachintha Shanmuganathan, Dhanya Aitken, Thomas Joo, Ji-Hoon E. Imran, Samira Shepherd, Rebecca Craig, Jeffrey M. Green, Mark Hiden, Ursula Novakovic, Boris Saffery, Richard |
author_sort | Weiss, Elisa |
collection | PubMed |
description | Inflammatory memory involves the molecular and cellular ‘reprogramming’ of innate immune cells following exogenous stimuli, leading to non-specific protection against subsequent pathogen exposure. This phenomenon has now also been described in non-hematopoietic cells, such as human fetal and adult endothelial cells. In this study we mapped the cell-specific DNA methylation profile and the transcriptomic remodelling during the establishment of inflammatory memory in two distinct fetal endothelial cell types – a progenitor cell (ECFC) and a differentiated cell (HUVEC) population. We show that both cell types have a core transcriptional response to an initial exposure to a viral-like ligand, Poly(I:C), characterised by interferon responsive genes. There was also an ECFC specific response, marked by the transcription factor ELF1, suggesting a non-canonical viral response pathway in progenitor endothelial cells. Next, we show that both ECFCs and HUVECs establish memory in response to an initial viral exposure, resulting in an altered subsequent response to lipopolysaccharide. While the capacity to train or tolerize the induction of specific sets of genes was similar between the two cell types, the progenitor ECFCs show a higher capacity to establish memory. Among tolerized cellular pathways are those involved in endothelial barrier establishment and leukocyte migration, both important for regulating systemic immune-endothelial cell interactions. These findings suggest that the capacity for inflammatory memory may be a common trait across different endothelial cell types but also indicate that the specific downstream targets may vary by developmental stage. |
format | Online Article Text |
id | pubmed-8640490 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86404902021-12-04 Transcriptomic Remodelling of Fetal Endothelial Cells During Establishment of Inflammatory Memory Weiss, Elisa Vlahos, Amanda Kim, Bowon Wijegunasekara, Sachintha Shanmuganathan, Dhanya Aitken, Thomas Joo, Ji-Hoon E. Imran, Samira Shepherd, Rebecca Craig, Jeffrey M. Green, Mark Hiden, Ursula Novakovic, Boris Saffery, Richard Front Immunol Immunology Inflammatory memory involves the molecular and cellular ‘reprogramming’ of innate immune cells following exogenous stimuli, leading to non-specific protection against subsequent pathogen exposure. This phenomenon has now also been described in non-hematopoietic cells, such as human fetal and adult endothelial cells. In this study we mapped the cell-specific DNA methylation profile and the transcriptomic remodelling during the establishment of inflammatory memory in two distinct fetal endothelial cell types – a progenitor cell (ECFC) and a differentiated cell (HUVEC) population. We show that both cell types have a core transcriptional response to an initial exposure to a viral-like ligand, Poly(I:C), characterised by interferon responsive genes. There was also an ECFC specific response, marked by the transcription factor ELF1, suggesting a non-canonical viral response pathway in progenitor endothelial cells. Next, we show that both ECFCs and HUVECs establish memory in response to an initial viral exposure, resulting in an altered subsequent response to lipopolysaccharide. While the capacity to train or tolerize the induction of specific sets of genes was similar between the two cell types, the progenitor ECFCs show a higher capacity to establish memory. Among tolerized cellular pathways are those involved in endothelial barrier establishment and leukocyte migration, both important for regulating systemic immune-endothelial cell interactions. These findings suggest that the capacity for inflammatory memory may be a common trait across different endothelial cell types but also indicate that the specific downstream targets may vary by developmental stage. Frontiers Media S.A. 2021-11-19 /pmc/articles/PMC8640490/ /pubmed/34867995 http://dx.doi.org/10.3389/fimmu.2021.757393 Text en Copyright © 2021 Weiss, Vlahos, Kim, Wijegunasekara, Shanmuganathan, Aitken, Joo, Imran, Shepherd, Craig, Green, Hiden, Novakovic and Saffery 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 | Immunology Weiss, Elisa Vlahos, Amanda Kim, Bowon Wijegunasekara, Sachintha Shanmuganathan, Dhanya Aitken, Thomas Joo, Ji-Hoon E. Imran, Samira Shepherd, Rebecca Craig, Jeffrey M. Green, Mark Hiden, Ursula Novakovic, Boris Saffery, Richard Transcriptomic Remodelling of Fetal Endothelial Cells During Establishment of Inflammatory Memory |
title | Transcriptomic Remodelling of Fetal Endothelial Cells During Establishment of Inflammatory Memory |
title_full | Transcriptomic Remodelling of Fetal Endothelial Cells During Establishment of Inflammatory Memory |
title_fullStr | Transcriptomic Remodelling of Fetal Endothelial Cells During Establishment of Inflammatory Memory |
title_full_unstemmed | Transcriptomic Remodelling of Fetal Endothelial Cells During Establishment of Inflammatory Memory |
title_short | Transcriptomic Remodelling of Fetal Endothelial Cells During Establishment of Inflammatory Memory |
title_sort | transcriptomic remodelling of fetal endothelial cells during establishment of inflammatory memory |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8640490/ https://www.ncbi.nlm.nih.gov/pubmed/34867995 http://dx.doi.org/10.3389/fimmu.2021.757393 |
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