Monocyte to macrophage differentiation goes along with modulation of the plasmalogen pattern through transcriptional regulation.

<h4>Background</h4>Dysregulation of monocyte-macrophage differentiation is a hallmark of vascular and metabolic diseases and associated with persistent low grade inflammation. Plasmalogens represent ether lipids that play a role in diabesity and previous data show diminished plasmalogen...

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Autores principales:	Stefan Wallner, Margot Grandl, Tatiana Konovalova, Alexander Sigrüner, Thomas Kopf, Markus Peer, Evelyn Orsó, Gerhard Liebisch, Gerd Schmitz
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c1b5e1c306804366adff0ad44d3bd11c
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spelling	oai:doaj.org-article:c1b5e1c306804366adff0ad44d3bd11c2021-11-18T08:24:18ZMonocyte to macrophage differentiation goes along with modulation of the plasmalogen pattern through transcriptional regulation.1932-620310.1371/journal.pone.0094102https://doaj.org/article/c1b5e1c306804366adff0ad44d3bd11c2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24714687/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Dysregulation of monocyte-macrophage differentiation is a hallmark of vascular and metabolic diseases and associated with persistent low grade inflammation. Plasmalogens represent ether lipids that play a role in diabesity and previous data show diminished plasmalogen levels in obese subjects. We therefore analyzed transcriptomic and lipidomic changes during monocyte-macrophage differentiation in vitro using a bioinformatic approach.<h4>Methods</h4>Elutriated monocytes from 13 healthy donors were differentiated in vitro to macrophages using rhM-CSF under serum-free conditions. Samples were taken on days 0, 1, 4 and 5 and analyzed for their lipidomic and transcriptomic profiles.<h4>Results</h4>Gene expression analysis showed strong regulation of lipidome-related transcripts. Enzymes involved in fatty acid desaturation and elongation were increasingly expressed, peroxisomal and ER stress related genes were induced. Total plasmalogen levels remained unchanged, while the PE plasmalogen species pattern became more similar to circulating granulocytes, showing decreases in PUFA and increases in MUFA. A partial least squares discriminant analysis (PLS/DA) revealed that PE plasmalogens discriminate the stage of monocyte-derived macrophage differentiation. Partial correlation analysis could predict novel potential key nodes including DOCK1, PDK4, GNPTAB and FAM126A that might be involved in regulating lipid and especially plasmalogen homeostasis during differentiation. An in silico transcription analysis of lipid related regulation revealed known motifs such as PPAR-gamma and KLF4 as well as novel candidates such as NFY, RNF96 and Zinc-finger proteins.<h4>Conclusion</h4>Monocyte to macrophage differentiation goes along with profound changes in the lipid-related transcriptome. This leads to an induction of fatty-acid desaturation and elongation. In their PE-plasmalogen profile macrophages become more similar to granulocytes than monocytes, indicating terminal phagocytic differentiation. Therefore PE plasmalogens may represent potential biomarkers for cell activation. For the underlying transcriptional network we were able to predict a range of novel central key nodes and underlying transcription factors using a bioinformatic approach.Stefan WallnerMargot GrandlTatiana KonovalovaAlexander SigrünerThomas KopfMarkus PeerEvelyn OrsóGerhard LiebischGerd SchmitzPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 4, p e94102 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Stefan Wallner Margot Grandl Tatiana Konovalova Alexander Sigrüner Thomas Kopf Markus Peer Evelyn Orsó Gerhard Liebisch Gerd Schmitz Monocyte to macrophage differentiation goes along with modulation of the plasmalogen pattern through transcriptional regulation.
description	<h4>Background</h4>Dysregulation of monocyte-macrophage differentiation is a hallmark of vascular and metabolic diseases and associated with persistent low grade inflammation. Plasmalogens represent ether lipids that play a role in diabesity and previous data show diminished plasmalogen levels in obese subjects. We therefore analyzed transcriptomic and lipidomic changes during monocyte-macrophage differentiation in vitro using a bioinformatic approach.<h4>Methods</h4>Elutriated monocytes from 13 healthy donors were differentiated in vitro to macrophages using rhM-CSF under serum-free conditions. Samples were taken on days 0, 1, 4 and 5 and analyzed for their lipidomic and transcriptomic profiles.<h4>Results</h4>Gene expression analysis showed strong regulation of lipidome-related transcripts. Enzymes involved in fatty acid desaturation and elongation were increasingly expressed, peroxisomal and ER stress related genes were induced. Total plasmalogen levels remained unchanged, while the PE plasmalogen species pattern became more similar to circulating granulocytes, showing decreases in PUFA and increases in MUFA. A partial least squares discriminant analysis (PLS/DA) revealed that PE plasmalogens discriminate the stage of monocyte-derived macrophage differentiation. Partial correlation analysis could predict novel potential key nodes including DOCK1, PDK4, GNPTAB and FAM126A that might be involved in regulating lipid and especially plasmalogen homeostasis during differentiation. An in silico transcription analysis of lipid related regulation revealed known motifs such as PPAR-gamma and KLF4 as well as novel candidates such as NFY, RNF96 and Zinc-finger proteins.<h4>Conclusion</h4>Monocyte to macrophage differentiation goes along with profound changes in the lipid-related transcriptome. This leads to an induction of fatty-acid desaturation and elongation. In their PE-plasmalogen profile macrophages become more similar to granulocytes than monocytes, indicating terminal phagocytic differentiation. Therefore PE plasmalogens may represent potential biomarkers for cell activation. For the underlying transcriptional network we were able to predict a range of novel central key nodes and underlying transcription factors using a bioinformatic approach.
format	article
author	Stefan Wallner Margot Grandl Tatiana Konovalova Alexander Sigrüner Thomas Kopf Markus Peer Evelyn Orsó Gerhard Liebisch Gerd Schmitz
author_facet	Stefan Wallner Margot Grandl Tatiana Konovalova Alexander Sigrüner Thomas Kopf Markus Peer Evelyn Orsó Gerhard Liebisch Gerd Schmitz
author_sort	Stefan Wallner
title	Monocyte to macrophage differentiation goes along with modulation of the plasmalogen pattern through transcriptional regulation.
title_short	Monocyte to macrophage differentiation goes along with modulation of the plasmalogen pattern through transcriptional regulation.
title_full	Monocyte to macrophage differentiation goes along with modulation of the plasmalogen pattern through transcriptional regulation.
title_fullStr	Monocyte to macrophage differentiation goes along with modulation of the plasmalogen pattern through transcriptional regulation.
title_full_unstemmed	Monocyte to macrophage differentiation goes along with modulation of the plasmalogen pattern through transcriptional regulation.
title_sort	monocyte to macrophage differentiation goes along with modulation of the plasmalogen pattern through transcriptional regulation.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/c1b5e1c306804366adff0ad44d3bd11c
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Monocyte to macrophage differentiation goes along with modulation of the plasmalogen pattern through transcriptional regulation.

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