Evidence map›Paper›PMID 40957877›Full record

ArticleNature communications2025

Multicolor fate mapping of microglia reveals polyclonal proliferation, heterogeneity, and cell-cell interactions after ischemic stroke in mice.

Majed Kikhia, Simone Schilling, Marie-Louise Herzog, Michelle Livne, Marcus Semtner, Tuan Leng Tay, Marco Prinz, Helmut Kettenmann, Matthias Endres, Golo Kronenberg and 2 more

Abstract read
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 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
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  3. Review
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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

12 authors.

Majed KikhiaCharité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurology with Experimental Neurology, Charitéplatz 1, 10117, Berlin, Germany.ORCID http://orcid.org/0000-0002-7719-9455
Simone SchillingCharité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurology with Experimental Neurology, Charitéplatz 1, 10117, Berlin, Germany.
Marie-Louise HerzogCharité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurology with Experimental Neurology, Charitéplatz 1, 10117, Berlin, Germany.
Michelle LivneCharité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurosurgery, Predictive Modelling in Medicine Research Group, Augustenburger Platz 1, 13353, Berlin, Germany.ORCID http://orcid.org/0000-0002-8277-4733
Marcus SemtnerMax-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Tuan Leng TayDepartment of Biology, Boston University, Boston, MA, USA.ORCID http://orcid.org/0000-0002-3507-6502
Marco PrinzInstitute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0002-0349-1955
Helmut KettenmannMax-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Matthias EndresCharité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurology with Experimental Neurology, Charitéplatz 1, 10117, Berlin, Germany.ORCID http://orcid.org/0000-0001-6520-3720
Golo KronenbergCharité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurology with Experimental Neurology, Charitéplatz 1, 10117, Berlin, Germany.
Ria Göttert *Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurology with Experimental Neurology, Charitéplatz 1, 10117, Berlin, Germany.ORCID http://orcid.org/0000-0003-4756-7381
Karen Gertz *Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurology with Experimental Neurology, Charitéplatz 1, 10117, Berlin, Germany. karen.gertz@charite.de.ORCID http://orcid.org/0000-0002-1203-641X

Funding

Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) CSBDeutsche Forschungsgemeinschaft (German Research Foundation) GE 2576/5-1
6 · The paper itself

Abstract

Microglial proliferation is a principal element of the inflammatory response to brain ischemia. However, the precise proliferation dynamics, phenotype acquisition, and functional consequences of newly emerging microglia are not yet understood. Using multicolor fate mapping and computational methods, we here demonstrate that microglia exhibit polyclonal proliferation in the ischemic lesion of female mice. The peak number of clones occurs at 14 days, while the largest clones are observed at 4 weeks post-stroke. Whole-cell patch-clamp recordings of microglia reveal a homogeneous acute response to ischemia with a pattern of outward and inward currents that evolves over time. In the resolution phase, 8 weeks post-stroke, microglial cells within one clone share similar membrane properties, while neighboring microglia from different clones display more heterogeneous electrophysiological profiles. Super-resolution microscopy and live-cell imaging unmask various forms of cell-cell interactions between microglial cells from different clones. Overall, this study demonstrates the polyclonal proliferation of microglia after cerebral ischemia and suggests that clonality contributes to their functional heterogeneity. Thus, targeting clones with specific functional phenotypes may have potential for future therapeutic modulation of microglia after stroke.

Indexed as

Brain IschemiaCell CommunicationIschemic StrokeMicrogliaStrokeAnimalsCell ProliferationDisease Models, AnimalFemaleMiceMice, Inbred C57BLPatch-Clamp Techniques

Identifiers

PMID40957877
PMCPMC12441135

What Socratic holds

Textmetadata
LicenceCC BY
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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.