Evidence map›Paper›PMID 41756450›Full record

ArticleResearch square2026

Epigenetic control of microglial developmental milestones from proliferative progenitors to efficient phagocytes.

Marta Pereira-Iglesias, Duncan Martinson, Carles Falco, Joel Maldonado-Teixido, Marco Gonzalez-Dominguez, Rodrigo Senovilla-Ganzo, Eva Benito, Sol Beccari, Jorge Valero, Bella Mora-Romero and 21 more

Abstract readPreprint
In one paragraph

Article in Research square, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

31 authors.

Marta Pereira-IglesiasAchucarro Basque Center for Neuroscience, Science Park University of the Basque Country EHU/UPV, Leioa, Spain.
Duncan MartinsonThe Francis Crick Institute, London, UK.ORCID 0000-0002-3590-606X
Carles FalcoMathematical Institute, Oxford University, Oxford, UK.
Joel Maldonado-TeixidoAchucarro Basque Center for Neuroscience, Science Park University of the Basque Country EHU/UPV, Leioa, Spain.
Marco Gonzalez-DominguezAchucarro Basque Center for Neuroscience, Science Park University of the Basque Country EHU/UPV, Leioa, Spain.
Rodrigo Senovilla-GanzoAchucarro Basque Center for Neuroscience, Science Park University of the Basque Country EHU/UPV, Leioa, Spain.
Eva BenitoAchucarro Basque Center for Neuroscience, Science Park University of the Basque Country EHU/UPV, Leioa, Spain.
Sol BeccariAchucarro Basque Center for Neuroscience, Science Park University of the Basque Country EHU/UPV, Leioa, Spain.
Jorge ValeroInstitute of Neuroscience of Castilla y León - INCyL, Universidad de Salamanca, Salamanca, Spain.ORCID 0000-0001-6072-3313
Bella Mora-RomeroInstituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Seville, Spain.
Ivan BallaschDepartament de Biomedicina, Facultat de Medicina, Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain.
Sarah ViguierCentre interdisciplinaire de recherche en biologie (CIRB), Collège de France, CNRS, Inserm, Université PSL Paris France.
Philipp HaneInstitute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
Molly BoettigerDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado, USA.ORCID 0009-0008-0244-0938
Julie A ReiszDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado, USA.
Alba Elías-TersaCentro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
Yasmina MansoCentro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
Laura ParkkinenNuffield Department of Clinical Neurosciences, University of Oxford, Level 6 West Wing, John Radcliffe Hospital, Oxford OX3 9DU, UK.0.
Ana María AransayCICbioGUNE, Genome analysis platform, Derio, Spain.ORCID 0000-0002-8271-612X
Federico N SoriaAchucarro Basque Center for Neuroscience, Science Park University of the Basque Country EHU/UPV, Leioa, Spain.
Angelo D'AlessandroDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado, USA.ORCID 0000-0002-2258-6490
Eduardo SorianoCentro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
Morgane S ThionCentre interdisciplinaire de recherche en biologie (CIRB), Collège de France, CNRS, Inserm, Université PSL Paris France.
Sonia GarelCentre interdisciplinaire de recherche en biologie (CIRB), Collège de France, CNRS, Inserm, Université PSL Paris France.
Melanie GreterInstitute of Experimental Immunology, University of Zurich, Zurich, Switzerland.ORCID 0000-0002-7220-5369
Albert GiraltDepartament de Biomedicina, Facultat de Medicina, Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain.
Alberto PascualInstituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Seville, Spain.ORCID 0000-0001-5459-6207
Fernando García-MorenoAchucarro Basque Center for Neuroscience, Science Park University of the Basque Country EHU/UPV, Leioa, Spain.ORCID 0000-0001-9048-4237
David A MenassaNuffield Department of Clinical Neurosciences, University of Oxford, Level 6 West Wing, John Radcliffe Hospital, Oxford OX3 9DU, UK.0.ORCID 0000-0002-5984-8407
Jose A CarrilloMathematical Institute, Oxford University, Oxford, UK.ORCID 0000-0001-8819-4660
Amanda SierraAchucarro Basque Center for Neuroscience, Science Park University of the Basque Country EHU/UPV, Leioa, Spain.ORCID 0000-0001-8415-096X

Funding

Dissecting the Etiology of The Lewy Body DementiasR01NS124848 · NINDS · J. DAVID GLADSTONE INSTITUTES · PI STEVEN M FINKBEINER · 2025 to 2026
$1.6M
NINDS NIH HHS R01 NS124848
6 · The paper itself

Abstract

Early immune perturbations increase the risk of brain disorders, yet the mechanisms underlying the functional maturation of microglia, the brain resident immune cells, remain poorly defined. Here, we used mathematical modeling of hippocampus and cerebellum to reconstruct postnatal microglial development. We identified a proliferative-to-quiescent (P/Q) switch around P3/P4 that preceded the acquisition of morphological complexity and efficient phagocytosis and was accompanied by changes in cell-cycle dynamics and metabolic state. This P/Q switch was recapitulated in repopulation contexts in mice and in the fetal human brain. Pharmacological and genetic perturbations of proliferation impaired subsequent morphological complexity and phagocytosis efficiency. Finally, microglial developmental maturation was associated with chromatin remodeling and driven by the epigenetic regulator Ikaros. These findings uncover the milestones of microglial development, revealing a potential period of early vulnerability and establishing an unexpected linkage between proliferation and phagocytosis essential to understanding how these processes are coordinated in neurodegenerative disorders.

Indexed as

Bayesian parameter inferencedevelopmentepigenetic modulatorsIkarosmicrogliaphagocytosispopulation modelingproliferation

Identifiers

PMID41756450
PMCPMC12934985

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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.