Evidence mapPaperPMID 41227333Full record

ArticleCells2025

Differential Responses of Human iPSC-Derived Microglia to Stimulation with Diverse Inflammogens.

Chiara Wolfbeisz, Julian Suess, Nadine Dreser, Heidrun Leisner, Markus Brüll, Madeleine Fandrich, Nicole Schneiderhan-Marra, Oliver Poetz, Thomas Hartung, Marcel Leist

Abstract read
In one paragraph

Article in Cells, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
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

10 authors.

Chiara WolfbeiszIn Vitro Toxicology and Biomedicine, Chair inaugurated by the Doerenkamp-Zbinden Foundation, University of Konstanz, 78464 Konstanz, Germany.
Julian SuessIn Vitro Toxicology and Biomedicine, Chair inaugurated by the Doerenkamp-Zbinden Foundation, University of Konstanz, 78464 Konstanz, Germany.
Nadine DreserIn Vitro Toxicology and Biomedicine, Chair inaugurated by the Doerenkamp-Zbinden Foundation, University of Konstanz, 78464 Konstanz, Germany.ORCID 0000-0002-7103-0990
Heidrun LeisnerIn Vitro Toxicology and Biomedicine, Chair inaugurated by the Doerenkamp-Zbinden Foundation, University of Konstanz, 78464 Konstanz, Germany.
Markus BrüllIn Vitro Toxicology and Biomedicine, Chair inaugurated by the Doerenkamp-Zbinden Foundation, University of Konstanz, 78464 Konstanz, Germany.
Madeleine FandrichNatural and Medical Sciences Institute, University of Tuebingen, 72074 Tuebingen, Germany.
Nicole Schneiderhan-MarraNatural and Medical Sciences Institute, University of Tuebingen, 72074 Tuebingen, Germany.
Oliver PoetzNatural and Medical Sciences Institute, University of Tuebingen, 72074 Tuebingen, Germany.ORCID 0000-0002-1189-9547
Thomas HartungCenter for Alternatives to Animal Testing (CAAT)-Europe, University of Konstanz, 78464 Konstanz, Germany.ORCID 0000-0003-1359-7689
Marcel LeistIn Vitro Toxicology and Biomedicine, Chair inaugurated by the Doerenkamp-Zbinden Foundation, University of Konstanz, 78464 Konstanz, Germany.ORCID 0000-0002-3778-8693

Funding

Pilot Project ProgramP30ES032756 · JOHNS HOPKINS UNIVERSITY · 2025 to 2025
$1.1M
European Chemical Industry Council LRI-AIMT 11European Union's Horizon 2020 research and innovation program 964537NIEHS NIH HHS P30 ES032756
6 · The paper itself

Abstract

Human microglia are central regulators and actors in brain infections and neuro-inflammatory pathologies. However, access to such cells is limited, and studies systematically mapping the spectrum of their inflammatory states are scarce. Here, we generated microglia-like cells (MGLCs) from human induced pluripotent stem cells and characterized them as a robust, accessible model system for studying inflammatory activation. We validated lineage identity through transcriptome profiling, revealing selective upregulation of microglial signature genes and enrichment of microglia/macrophage-related gene sets. MGLCs displayed distinct morphologies and produced stimulus- and time-dependent cytokine secretion profiles upon exposure to diverse inflammatory stimuli, including pro-inflammatory cytokines (TNFα, interferon-γ) and agonists of the Toll-like receptors TLR2 (FSL-1), TLR3 (Poly(I:C)), TLR4 (lipopolysaccharide, LPS), and TLR7 (imiquimod). Transcriptome profiling and bioinformatics analysis revealed distinct activation signatures. Functional assays demonstrated stimulus-specific engagement of NFκB and JAK-STAT signaling pathways. The shared NFκB nuclear translocation response of TLR ligands and TNFα was reflected in overlapping transcriptome profiles: they shared modules (e.g., oxidative stress response and TNFα-related signaling) identified by weighted gene co-expression network analysis. Finally, the potential consequences of microglia activation for neighboring cells were studied on the example of microglia-astrocyte crosstalk. The capacity of MGLC supernatants to stimulate astrocytes was measured by quantifying astrocytic NFκB translocation. MGLCs stimulated with FSL-1, LPS, or Poly(I:C) indirectly activated astrocytes via a strictly TNFα-dependent mechanism, highlighting the role of soluble mediators in the signal propagation. Altogether, this platform enables a dissection of microglia activation states and multi-parametric characterization of subsequent neuroinflammation.

Indexed as

Induced Pluripotent Stem CellsInflammationMicrogliaCytokinesGene Expression ProfilingHumansNF-kappa BSignal TransductionToll-Like ReceptorsTranscriptomeTumor Necrosis Factor-alphaCytokinesNF-kappa BToll-Like ReceptorsTumor Necrosis Factor-alphaastrocytescytokine release(neuro-)inflammationTLRTNFαtranscriptome changes

Identifiers

PMID41227333
PMCPMC12607375

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.