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Cell Surface Markers Identify Astrocyte Subpopulations in the Adult Hippocampus With a Heterogeneous Response to Aging.

Overview

Authors: Lucía Casares‐Crespo1,2, Marife Cano‐Jaimez1,2, Raquel Anta1, Alba Ripollés‐Boix1, Fabián Robledo‐Yagüe3, Sheila Zúñiga‐Trejos3, Helena Mira1,2
  1. Instituto de Biomedicina de Valencia (IBV), CSIC València Spain
  2. Valencia Biomedical Research Foundation Centro de Investigación Príncipe Felipe (CIPF)—Associated Unit to the IBV‐CSIC València Spain
  3. Bioinformatics Unit INCLIVA Biomedical Research Institute València Spain
Journal: Glia, volume 74, issue 11, article e70236
Dates: received 14 November 2025; accepted 15 September 2026; published online 24 September 2026; in print November 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1002/glia.70236 · PMID 42786753 · PMCID PMC13613007 · OpenAlex W4416049338
Open access: hybrid, a free copy (OpenAlex)
Categories: genetics / omics (modality), mouse (organism), cellular / molecular (subfield)
Methods: Statistics, Connectivity, fMRI & imaging
Keywords: ACSA‐2, aging, astrocyte diversity, GLAST, hippocampus, protocadherin
MeSH: Aging*, Astrocytes*, Hippocampus*, Animals, Biomarkers, Cells, Cultured, Coculture Techniques, Excitatory Amino Acid Transporter 1, Male, Mice, Mice, Inbred C57BL, Neurons (* major topic)
Topic: Neuroscience and Neuropharmacology Research (Cellular and Molecular Neuroscience, Neuroscience), according to OpenAlex
Funding: Spanish Ministry of Science and Innovation (PID2019‐111225RB‐I00, PID2022‐141707NBI00); Generalitat Valenciana (CIAICO/2022/74)
Citations: not cited yet (Europe PMC); 69 references in the paper

Abstract

Astrocyte diversity is currently expanding both between and within specific brain regions. Here, we assessed the spatial distribution and transcriptomic profile of two hippocampal astrocyte subpopulations, defined by combinatorial expression of the cell surface astrocyte markers ACSA‐1 or GLAST/SLC1A3, and ACSA‐2 or ATP1B2. Fluorescence activated cell sorting and genome‐wide transcriptomics by bulk RNAseq uncovered distinct transcriptional signatures of the two astrocyte subsets and highlighted heterogeneous responses during aging. The most abundant ATP1B2/GLAST double‐positive astrocytes corresponded to functionally specialized glial cells with increased protein glycosylation and stable gene expression patterns. Signatures related to mitochondrial respiration and cholesterol metabolism were induced during aging in ATP1B2 single‐positive astrocytes, while cell adhesion genes from the γ‐protocadherin cluster were repressed in double‐positive astrocytes. Heterochronic co‐culture assays with primary neurons show the loss of synaptogenic function of old ATP1B2/GLAST astrocytes. Our results complement previous studies demonstrating the presence of morphological and molecular astrocyte heterogeneity within the hippocampus, and uncover differences among astrocyte subsets in their transcriptomic response to aging.

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

Code

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Data

Datasets cited

Data Availability Statement

The data that support the findings of this study are openly available in ArrayExpress database (EMBL‐EBI) at https://www.ebi.ac.uk/biostudies/arrayexpress/studies/E‐MTAB‐15811?key=e815a643‐433d‐49be‐94a6‐ba4682444380 (https://www.ebi.ac.uk/biostudies/arrayexpress/studies/E-MTAB-15811?key=e815a643-433d-49be-94a6-ba4682444380), reference number E‐MTAB‐15811.

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

Versions

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Version 1, 1 November 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 7 authors, 6 keywords, 12 MeSH terms, 2 funders, 65 references.

Cite

This paper

Casares‐Crespo, L., Cano‐Jaimez, M., Anta, R., Ripollés‐Boix, A., Robledo‐Yagüe, F., Zúñiga‐Trejos, S., & Mira, H. (2026). Cell Surface Markers Identify Astrocyte Subpopulations in the Adult Hippocampus With a Heterogeneous Response to Aging. Glia, 74(11), e70236. https://doi.org/10.1002/glia.70236

BibTeX

@article{casarescrespo2026cell,
author = {Casares‐Crespo, Lucía and Cano‐Jaimez, Marife and Anta, Raquel and Ripollés‐Boix, Alba and Robledo‐Yagüe, Fabián and Zúñiga‐Trejos, Sheila and Mira, Helena},
title = {{Cell Surface Markers Identify Astrocyte Subpopulations in the Adult Hippocampus With a Heterogeneous Response to Aging}},
journal = {Glia},
year = {2026},
month = nov,
volume = {74},
number = {11},
pages = {e70236},
publisher = {Wiley},
issn = {0894-1491},
doi = {10.1002/glia.70236},
url = {https://doi.org/10.1002/glia.70236},
pmid = {42786753},
pmcid = {PMC13613007}
}

RIS

TY - JOUR
AU - Casares‐Crespo, Lucía
AU - Cano‐Jaimez, Marife
AU - Anta, Raquel
AU - Ripollés‐Boix, Alba
AU - Robledo‐Yagüe, Fabián
AU - Zúñiga‐Trejos, Sheila
AU - Mira, Helena
TI - Cell Surface Markers Identify Astrocyte Subpopulations in the Adult Hippocampus With a Heterogeneous Response to Aging
T2 - Glia
J2 - Glia
PY - 2026
DA - 2026/11/01
VL - 74
IS - 11
SP - e70236
SN - 0894-1491
PB - Wiley
DO - 10.1002/glia.70236
UR - https://doi.org/10.1002/glia.70236
LA - en
ER -

CSL-JSON

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