Evidence map›Paper›PMID 41350273›Full record

ArticleNature communications2025

Human oligodendrocyte progenitor cells mediate synapse elimination through TAM receptor activation.

Asimenia Gkogka, Susmita Malwade, Marja Koskuvi, Sohvi Ohtonen, Ellinor Molnar, Raj Bose, Sandra Ceccatelli, Jari Koistinaho, Jari Tiihonen, Martin Schalling and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 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. Glial Control of Cortical Neuronal Circuit Maturation and Plasticity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024
    Review
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

12 authors.

Asimenia GkogkaDepartment of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0009-0001-7892-0769
Susmita MalwadeDepartment of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-6756-018X
Marja KoskuviDepartment of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Sohvi OhtonenDepartment of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Ellinor MolnarDepartment of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Raj BoseDepartment of Neuroscience, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0009-0008-4039-862X
Sandra CeccatelliDepartment of Neuroscience, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-9367-8480
Jari KoistinahoNeuroscience Center, HiLIFE, and Drug Research Program, Division of Pharmacology and Pharmacotherapy, University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0001-6559-1153
Jari TiihonenNeuroscience Center, HiLIFE, and Drug Research Program, Division of Pharmacology and Pharmacotherapy, University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0002-0400-6798
Martin SchallingDepartment of Molecular Medicine and Surgery, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.ORCID http://orcid.org/0000-0001-5011-2922
Samudyata SamudyataDepartment of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-1062-2626
Carl M SellgrenDepartment of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. carl.sellgren@ki.se.ORCID http://orcid.org/0000-0001-9103-2785

Funding

Hjärnfonden (Swedish Brain Foundation) FO2022-0135Stockholms Läns Landsting (Stockholm County Council) 2017-02559
6 · The paper itself

Abstract

Oligodendrocyte progenitor cells (OPCs) have been implicated in synaptic remodelling in animal models, but the underlying mechanisms and their relevance to human brain development remain unclear. Here, we generate a human multi-lineage forebrain organoid model in which OPCs, together with microglia, form close contacts with synapses and spontaneously internalize synaptic material. Single-nucleus transcriptomic profiling with unbiased cell-cell communication analysis identifies the growth arrest-specific gene 6 (GAS6)-TYRO3, AXL, and MERTK (TAM) receptor axis as a key signalling pathway, with neurons and microglia expressing GAS6 and a subset of OPCs expressing AXL. Further, dose-dependent pharmacological inhibition of TAM receptors demonstrates the importance of AXL, and targeted reduction of AXL expression in OPCs impairs synaptic uptake. These findings reveal a role for GAS6-AXL signalling in driving synaptic internalisation by AXL+ OPCs during early human brain development.

Indexed as

Oligodendrocyte Precursor CellsProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesSynapsesAnimalsAxl Receptor Tyrosine KinaseCell Communicationc-Mer Tyrosine KinaseGrowth Arrest-Specific Protein 6HumansIntercellular Signaling Peptides and ProteinsMicrogliaNeuronsOrganoidsProsencephalonSignal TransductionAXL protein, humanAxl Receptor Tyrosine Kinasec-Mer Tyrosine KinaseGrowth Arrest-Specific Protein 6Intercellular Signaling Peptides and ProteinsMERTK protein, humanProto-Oncogene ProteinsReceptor Protein-Tyrosine Kinases

Identifiers

PMID41350273
PMCPMC12680777

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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.