Evidence map›Paper›PMID 24714687›Full record

ArticlePloS one2014

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

Stefan Wallner, Margot Grandl, Tatiana Konovalova, Alexander Sigrüner, Thomas Kopf, Markus Peer, Evelyn Orsó, Gerhard Liebisch, Gerd Schmitz

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
1.6field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 51 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Stefan WallnerInstitute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, University of Regensburg, Regensburg, Germany.
Margot GrandlInstitute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, University of Regensburg, Regensburg, Germany.
Tatiana KonovalovaInstitute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, University of Regensburg, Regensburg, Germany.
Alexander SigrünerInstitute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, University of Regensburg, Regensburg, Germany.
Thomas KopfInstitute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, University of Regensburg, Regensburg, Germany.
Markus PeerInstitute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, University of Regensburg, Regensburg, Germany.
Evelyn OrsóInstitute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, University of Regensburg, Regensburg, Germany.
Gerhard LiebischInstitute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, University of Regensburg, Regensburg, Germany.
Gerd SchmitzInstitute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, University of Regensburg, Regensburg, Germany.
University Hospital Regensburg · DEUniversity of Regensburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDysregulation 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.

methodsElutriated 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.

resultsGene 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.

conclusionMonocyte 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.

Indexed as

Cell DifferentiationGene Expression RegulationHumansKruppel-Like Factor 4MacrophagesMonocytesPlasmalogensTranscriptomeKLF4 protein, humanKruppel-Like Factor 4Plasmalogens

Identifiers

PMID24714687
PMCPMC3979739
OpenAlexW2006351227

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.