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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\u20101 or GLAST\/SLC1A3, and ACSA\u20102 or ATP1B2. Fluorescence activated cell sorting and genome\u2010wide 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\u2010positive 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\u2010positive astrocytes, while cell adhesion genes from the \u03b3\u2010protocadherin cluster were repressed in double\u2010positive astrocytes. Heterochronic co\u2010culture 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.<\/jats:p>","DOI":"10.1002\/glia.70236","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T06:07:24Z","timestamp":1790316444000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cell Surface Markers Identify Astrocyte Subpopulations in the Adult Hippocampus With a Heterogeneous Response to Aging"],"prefix":"10.1002","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3854-3636","authenticated-orcid":false,"given":"Luc\u00eda","family":"Casares\u2010Crespo","sequence":"first","affiliation":[{"name":"Instituto de Biomedicina de Valencia (IBV), CSIC  Val\u00e8ncia Spain"},{"name":"Valencia Biomedical Research Foundation Centro de Investigaci\u00f3n Pr\u00edncipe Felipe (CIPF)\u2014Associated Unit to the IBV\u2010CSIC  Val\u00e8ncia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marife","family":"Cano\u2010Jaimez","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Valencia (IBV), CSIC  Val\u00e8ncia Spain"},{"name":"Valencia Biomedical Research Foundation Centro de Investigaci\u00f3n Pr\u00edncipe Felipe (CIPF)\u2014Associated Unit to the IBV\u2010CSIC  Val\u00e8ncia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4069-6723","authenticated-orcid":false,"given":"Raquel","family":"Anta","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Valencia (IBV), CSIC  Val\u00e8ncia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0430-7102","authenticated-orcid":false,"given":"Alba","family":"Ripoll\u00e9s\u2010Boix","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Valencia (IBV), CSIC  Val\u00e8ncia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabi\u00e1n","family":"Robledo\u2010Yag\u00fce","sequence":"additional","affiliation":[{"name":"Bioinformatics Unit INCLIVA Biomedical Research Institute  Val\u00e8ncia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3272-7605","authenticated-orcid":false,"given":"Sheila","family":"Z\u00fa\u00f1iga\u2010Trejos","sequence":"additional","affiliation":[{"name":"Bioinformatics Unit INCLIVA Biomedical Research Institute  Val\u00e8ncia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8574-9544","authenticated-orcid":false,"given":"Helena","family":"Mira","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Valencia (IBV), CSIC  Val\u00e8ncia Spain"},{"name":"Valencia Biomedical Research Foundation Centro de Investigaci\u00f3n Pr\u00edncipe Felipe (CIPF)\u2014Associated Unit to the IBV\u2010CSIC  Val\u00e8ncia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"Andrews S.2010.\u201cFastQC: A Quality Control Tool for High Throughput Sequence Data.\u201dhttp:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc\/."},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201014198\u20108"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010020\u20100602\u20101"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2017.04.030"},{"key":"e_1_2_10_6_1","unstructured":"Blighe K. 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