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Signaling cascades shape functional subpopulations of cortical astrocytes in male wild-type mice and APP/PS1dE9 Alzheimer's disease model.

Overview

Authors: Yiannis Poulot-Becq-Giraudon1,2, Océane Guillemaud2, Elisa Degl’Innocenti1, Vivien Letenneur2, Karouna Bascarane1,2, Tony Barbay3, Mie Møller Clausen2, Céline Derbois4, Martine Guillermier1,2, Ludmila Juricek2, Miriam Riquelme-Perez2,4, Tom Lakomy1,2, Lucile Benhaim1,2, Noëlle Dufour2, Pauline Gipchtein2, Fanny Petit2, Léa Siron1, Gwennaëlle Aurégan2, Nathalie Dechamps5,6, Marie-Claude Gaillard2
and 9 other authorsAlexis-Pierre Bemelmans2, Rémi Bos3, Maria-Angeles Carrillo-de Sauvage1,2, Giampaolo Milior7, Nathalie Rouach7, Solène Brohard4, Kevin Muret4, Eric Bonnet4, Carole Escartin1,2
ORCID iDs: Yiannis Poulot-Becq-Giraudon, Elisa Degl’Innocenti, Tony Barbay, Mie Møller Clausen, Miriam Riquelme-Perez, Tom Lakomy, Alexis-Pierre Bemelmans, Rémi Bos, Maria-Angeles Carrillo-de Sauvage, Giampaolo Milior, Nathalie Rouach, Solène Brohard, Kevin Muret, Eric Bonnet, Carole Escartin
  1. Université Paris-Saclay, CNRS, NeuroPSI, Saclay, France
  2. Université Paris-Saclay, CEA, CNRS, MIRCen, Laboratoire des Maladies Neurodégénératives, Fontenay-aux-Roses, France
  3. Aix Marseille Université, CNRS, Institut de Neurosciences de la Timone (INT), Marseille, France
  4. Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine (CNRGH), Evry, France
  5. Université Paris Cité, Inserm, CEA, Stabilité Génétique Cellules Souches et Radiations, iRCM/IBFJ, Fontenay-aux-Roses, France
  6. Université Paris-Saclay, Inserm, CEA, Stabilité Génétique Cellules Souches et Radiations,iRCM/IBFJ, Fontenay-aux-Roses, France
  7. Collège de France, CNRS, INSERM, PSL-NEURO, Université PSL, Paris, France
Institutions: Centre National de la Recherche Scientifique (France); Commissariat à l'Énergie Atomique et aux Énergies Alternatives (France); Université Paris-Saclay (France); Institut des Neurosciences Paris-Saclay (France); Laboratoire des Maladies Neurodégénératives (France); Molecular Imaging Research Center (France); Aix-Marseille Université (France); Institut de Neurosciences de la Timone (France); Centre National de Recherche en Génomique Humaine (France); Inserm (France); Université Paris Cité (France); CEA Paris-Saclay - Etablissement de Fontenay-aux-roses (France); Stabilité Génétique, Cellules Souches et Radiations (France); Collège de France (France); Université Paris Sciences et Lettres (France)
Journal: Nature communications, volume 17, issue 1, article 4194
Dates: received 27 March 2025; accepted 25 March 2026; published online 14 April 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41467-026-71826-w · PMID 41980951 · PMCID PMC13153161 · OpenAlex W7154360709
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: human (organism), mouse (organism), Alzheimer's / dementia (population), cellular / molecular (subfield)
Methods: Statistics, Evoked potentials, Connectivity
Keywords: Astrocyte, Cellular neuroscience, Alzheimer's disease
MeSH: Alzheimer Disease*, Astrocytes*, Signal Transduction*, Amyloid beta-Protein Precursor, Animals, Cerebral Cortex, Disease Models, Animal, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, NF-kappa B, Plaque, Amyloid, Prefrontal Cortex, Presenilin-1, STAT3 Transcription Factor (* major topic)
Topic: Neuroinflammation and Neurodegeneration Mechanisms (Neurology, Neuroscience), according to OpenAlex
Funding: Agence Nationale de la Recherche (ANR-10-IDEX-0001, ANR-16-TERC-0016-01 and ANR21-CE17-0047-02); Association France Alzheimer (6173); Fondation pour la Recherche Médicale (Foundation for Medical Research in France) (EQU202303016285)
Citations: cited by 2 papers (Europe PMC); 72 references in the paper

Abstract

Astrocytes are key partners for neurons and can impact diseases such as Alzheimer’s disease (AD), as they exhibit multiple reactive changes. Recent single cell/nucleus genomics analyses evidence astrocyte subpopulations coexisting in normal and AD brains. However, the signaling cascades controlling them, their functional characteristics and roles in AD are still unknown. Here, thanks to astrocyte-specific reporters for STAT3 and NF-kB signaling pathways, two regulators of astrocyte reactivity, we report the presence of three astrocyte subpopulations defined by their signaling activity, in the prefrontal cortex of male APP/PS1dE9 mice. These subpopulations are not triggered by amyloid deposition and are also observed in wild-type mice. They show distinct morphologies, molecular signatures and functional profiles. While NF-kB+ astrocytes have larger territories and higher lysosomal activity, STAT3+ astrocytes display enhanced hemichannel activity. Specific inhibition of these subpopulations reduces amyloid plaque size and impacts anxiety, social preference and social memory in AD but not wild-type mice. Our results show how innate signaling shapes astrocyte subpopulations in the mouse cortex, with distinct functions in health and disease.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

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Data

Datasets cited

Data availability

RNA-seq dataset is available on Gene Expression Omnibus under reference GSE290101 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE290101). All Source data are provided as a Source Data file. Raw data or images are available from the corresponding author upon request. Source data are provided with this paper.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 29 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 29 authors, 3 keywords, 17 MeSH terms, 3 funders, 71 references.

Cite

This paper

Poulot-Becq-Giraudon, Y., Guillemaud, O., Degl’Innocenti, E., Letenneur, V., Bascarane, K., Barbay, T., Møller Clausen, M., Derbois, C., Guillermier, M., Juricek, L., Riquelme-Perez, M., Lakomy, T., Benhaim, L., Dufour, N., Gipchtein, P., Petit, F., Siron, L., Aurégan, G., Dechamps, N., . . . Escartin, C. (2026). Signaling cascades shape functional subpopulations of cortical astrocytes in male wild-type mice and APP/PS1dE9 Alzheimer's disease model. Nature communications, 17(1), 4194. https://doi.org/10.1038/s41467-026-71826-w

BibTeX

@article{poulotbecqgiraudon2026signaling,
author = {Poulot-Becq-Giraudon, Yiannis and Guillemaud, Océane and Degl’Innocenti, Elisa and Letenneur, Vivien and Bascarane, Karouna and Barbay, Tony and Møller Clausen, Mie and Derbois, Céline and Guillermier, Martine and Juricek, Ludmila and Riquelme-Perez, Miriam and Lakomy, Tom and Benhaim, Lucile and Dufour, Noëlle and Gipchtein, Pauline and Petit, Fanny and Siron, Léa and Aurégan, Gwennaëlle and Dechamps, Nathalie and Gaillard, Marie-Claude and Bemelmans, Alexis-Pierre and Bos, Rémi and Carrillo-de Sauvage, Maria-Angeles and Milior, Giampaolo and Rouach, Nathalie and Brohard, Solène and Muret, Kevin and Bonnet, Eric and Escartin, Carole},
title = {{Signaling cascades shape functional subpopulations of cortical astrocytes in male wild-type mice and APP/PS1dE9 Alzheimer's disease model}},
journal = {Nature communications},
year = {2026},
month = apr,
volume = {17},
number = {1},
pages = {4194},
publisher = {Nature Publishing Group},
issn = {2041-1723},
doi = {10.1038/s41467-026-71826-w},
url = {https://doi.org/10.1038/s41467-026-71826-w},
pmid = {41980951},
pmcid = {PMC13153161}
}

RIS

TY - JOUR
AU - Poulot-Becq-Giraudon, Yiannis
AU - Guillemaud, Océane
AU - Degl’Innocenti, Elisa
AU - Letenneur, Vivien
AU - Bascarane, Karouna
AU - Barbay, Tony
AU - Møller Clausen, Mie
AU - Derbois, Céline
AU - Guillermier, Martine
AU - Juricek, Ludmila
AU - Riquelme-Perez, Miriam
AU - Lakomy, Tom
AU - Benhaim, Lucile
AU - Dufour, Noëlle
AU - Gipchtein, Pauline
AU - Petit, Fanny
AU - Siron, Léa
AU - Aurégan, Gwennaëlle
AU - Dechamps, Nathalie
AU - Gaillard, Marie-Claude
AU - Bemelmans, Alexis-Pierre
AU - Bos, Rémi
AU - Carrillo-de Sauvage, Maria-Angeles
AU - Milior, Giampaolo
AU - Rouach, Nathalie
AU - Brohard, Solène
AU - Muret, Kevin
AU - Bonnet, Eric
AU - Escartin, Carole
TI - Signaling cascades shape functional subpopulations of cortical astrocytes in male wild-type mice and APP/PS1dE9 Alzheimer's disease model
T2 - Nature communications
J2 - Nat Commun
PY - 2026
DA - 2026/04/14
VL - 17
IS - 1
SP - 4194
SN - 2041-1723
PB - Nature Publishing Group
DO - 10.1038/s41467-026-71826-w
UR - https://doi.org/10.1038/s41467-026-71826-w
LA - en
ER -

CSL-JSON

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}

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