Transcriptomic Remodelling of Fetal Endothelial Cells During Establishment of Inflammatory Memory Weiss, E, Vlahos, A, Kim, B, Wijegunasekara, S, Shanmuganathan, D, Aitken, T, Joo, JHE, Imran, S, Shepherd, R, Craig, Jeffrey, Green, M, Hiden, U, Novakovic, B and Saffery, R 2021, Transcriptomic Remodelling of Fetal Endothelial Cells During Establishment of Inflammatory Memory, Frontiers in Immunology, vol. 12, pp. 1-14, doi: 10.3389/fimmu.2021.757393. Attached Files Name Description MIMEType Size Downloads Title Transcriptomic Remodelling of Fetal Endothelial Cells During Establishment of Inflammatory Memory Author(s) Weiss, E Vlahos, A Kim, B Wijegunasekara, S Shanmuganathan, D Aitken, T Joo, JHE Imran, S Shepherd, R Craig, Jeffrey orcid.org/0000-0003-3979-7849 Green, M Hiden, U Novakovic, B Saffery, R Journal name Frontiers in Immunology Volume number 12 Article ID 757393 Start page 1 End page 14 Total pages 14 Publisher Frontiers Media Place of publication Lausanne, Switzerland Publication date 2021-11 ISSN 1664-3224 1664-3224 Keyword(s) endothelial cells endothelial progenitor cell HUVEC (human umbilical vein endothelial cells) inflammation inflammatory memory innate immune memory trained immunity transcriptome (RNA-seq) Summary 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. Language eng DOI 10.3389/fimmu.2021.757393 Indigenous content off Field of Research 1107 Immunology 1108 Medical Microbiology HERDC Research category C1 Refereed article in a scholarly journal Free to Read? Yes Persistent URL http://hdl.handle.net/10536/DRO/DU:30160411 Document type: Journal Article Collections: Faculty of Health School of Medicine Open Access Collection Related Links Link Description Link to full-text (open access)   Connect to Elements publication management system Go to link with your DU access privileges     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au. Versions Version Filter Type Fri, 31 Dec 2021, 13:56:19 EST Fri, 31 Dec 2021, 14:50:59 EST Tue, 18 Jan 2022, 16:37:29 EST Tue, 08 Feb 2022, 15:38:42 EST Tue, 08 Feb 2022, 16:13:57 EST Tue, 08 Feb 2022, 16:16:43 EST Thu, 10 Feb 2022, 08:58:27 EST Sat, 05 Mar 2022, 01:30:40 EST Filtered Full Citation counts:   Cited 0 times in TR Web of Science Cited 0 times in Scopus Search Google Scholar Access Statistics: 17 Abstract Views, 0 File Downloads  -  Detailed Statistics Created: Fri, 31 Dec 2021, 13:56:19 EST