{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:18:59Z","timestamp":1785424739644,"version":"3.56.0"},"posted":{"date-parts":[[2025,7,31]]},"group-title":"Neuroscience","reference-count":91,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01AG066198"],"award-info":[{"award-number":["R01AG066198"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 AG077636"],"award-info":[{"award-number":["R01 AG077636"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 AG075992"],"award-info":[{"award-number":["R01 AG075992"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 AG057565"],"award-info":[{"award-number":["R01 AG057565"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/00x0ma614","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,7,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Pharmacological activation of brain Retinoid X Receptors (RXRs) enhances cognition and facilitates amyloid-beta (A\u03b2) clearance in Alzheimer\u2019s disease (AD) mouse models, partly by upregulating Apolipoprotein E (\n                  <jats:italic>Apoe<\/jats:italic>\n                  ), a major AD genetic risk factor. However, the specific cellular contributions to these effects are unclear. Here, we used single-cell transcriptomic profiling to investigate cell subpopulation-specific responses to bexarotene, an RXR agonist, in APP\/PS1 mice. Our analysis revealed that bexarotene activated cholesterol biosynthesis and lipid metabolism transcriptional programs in homeostatic astrocytes and oligodendrocytes. Astrocytes also upregulated neurodevelopmental genes, while oligodendrocytes and endothelial cells showed enhanced protein folding and cellular growth pathways. Bexarotene further modulated immune responses, promoting A\u03b2-responsive signatures in disease-associated microglia and reactive astrocytes, while dampening pro-inflammatory responses in homeostatic microglia and endothelial cells. Furthermore,\n                  <jats:italic>Apoe<\/jats:italic>\n                  expression was significantly elevated across multiple cell types, especially in microglia and oligodendrocytes. Cell-cell communication analysis highlighted increased astrocyte-centered signaling, with APOE-driven pathways emerging as a prominent mediator. These findings clarify the cell-specific complexity of RXR-mediated regulation and underscore APOE as a central mediator of bexarotene\u2019s neuroprotective effects. This study provides mechanistic insights into RXR-targeted interventions, and supports APOE-associated pathways as promising therapeutic targets in AD.\n                <\/jats:p>","DOI":"10.1101\/2025.07.25.666575","type":"posted-content","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T14:00:25Z","timestamp":1753970425000},"source":"Crossref","is-referenced-by-count":1,"title":["Brain single-cell transcriptional responses to bexarotene-activated RXR in Alzheimer\u2019s disease model"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1685-011X","authenticated-orcid":false,"given":"Carolina","family":"Saibro-Girardi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6938-6536","authenticated-orcid":false,"given":"Nicholas F.","family":"Fitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5254-0509","authenticated-orcid":false,"given":"Daniel P.","family":"Gelain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0249-0280","authenticated-orcid":false,"given":"Iliya","family":"Lefterov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6761-0984","authenticated-orcid":false,"given":"Radosveta","family":"Koldamova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025080117105391000_2025.07.25.666575v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00269-y"},{"key":"2025080117105391000_2025.07.25.666575v1.2","doi-asserted-by":"crossref","unstructured":"Wolfe CM , Fitz NF , Nam KN , Lefterov I , Koldamova R . The Role of APOE and TREM2 in Alzheimer\u2019s Disease-Current Understanding and Perspectives. Int J Mol Sci. 2018;20(1).","DOI":"10.3390\/ijms20010081"},{"key":"2025080117105391000_2025.07.25.666575v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2022.01.002"},{"key":"2025080117105391000_2025.07.25.666575v1.4","unstructured":"Amany M , Kevan S , Elena Posse de C . The Mevalonate Pathway in Alzheimer\u2019s Disease \u2014 Cholesterol and Non-Sterol Isoprenoids. In: Inga Z , editor. Alzheimer\u2019s Disease. Rijeka: IntechOpen; 2015. p. Ch. 7."},{"issue":"4","key":"2025080117105391000_2025.07.25.666575v1.5","doi-asserted-by":"crossref","first-page":"839","DOI":"10.3233\/JAD-2011-111037","article-title":"Endoplasmic reticulum stress induces tau pathology and forms a vicious cycle: implication in Alzheimer\u2019s disease pathogenesis","volume":"28","year":"2012","journal-title":"J Alzheimers Dis"},{"key":"2025080117105391000_2025.07.25.666575v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2017.188.Blood"},{"key":"2025080117105391000_2025.07.25.666575v1.7","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24647"},{"key":"2025080117105391000_2025.07.25.666575v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2023.01.002"},{"issue":"18","key":"2025080117105391000_2025.07.25.666575v1.9","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1111\/bph.14668","article-title":"Therapeutic targeting of nuclear receptors, liver X and retinoid X receptors, for Alzheimer\u2019s disease","volume":"176","year":"2019","journal-title":"Br J Pharmacol"},{"key":"2025080117105391000_2025.07.25.666575v1.10","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-021-02709-y"},{"key":"2025080117105391000_2025.07.25.666575v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.03.012"},{"key":"2025080117105391000_2025.07.25.666575v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/srep42270"},{"issue":"10","key":"2025080117105391000_2025.07.25.666575v1.13","doi-asserted-by":"crossref","first-page":"e0223578","DOI":"10.1371\/journal.pone.0223578","article-title":"Bexarotene therapy ameliorates behavioral deficits and induces functional and molecular changes in very-old Triple Transgenic Mice model of Alzheime\u0155s disease","volume":"14","year":"2019","journal-title":"PLoS One"},{"key":"2025080117105391000_2025.07.25.666575v1.14","doi-asserted-by":"publisher","DOI":"10.1126\/science.1217697"},{"key":"2025080117105391000_2025.07.25.666575v1.15","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5198-13.2014"},{"key":"2025080117105391000_2025.07.25.666575v1.16","doi-asserted-by":"publisher","DOI":"10.1126\/science.340.6135.924-a"},{"key":"2025080117105391000_2025.07.25.666575v1.17","doi-asserted-by":"publisher","DOI":"10.1126\/science.340.6135.924-a"},{"key":"2025080117105391000_2025.07.25.666575v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2015.05.019"},{"key":"2025080117105391000_2025.07.25.666575v1.19","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1432-5"},{"key":"2025080117105391000_2025.07.25.666575v1.20","doi-asserted-by":"crossref","unstructured":"Dickey AS , Sanchez DN , Arreola M , Sampat KR , Fan W , Arbez N , et al. PPAR\u03b4 activation by bexarotene promotes neuroprotection by restoring bioenergetic and quality control homeostasis. Sci Transl Med. 2017;9(419).","DOI":"10.1126\/scitranslmed.aal2332"},{"issue":"2","key":"2025080117105391000_2025.07.25.666575v1.21","doi-asserted-by":"crossref","first-page":"e0172161","DOI":"10.1371\/journal.pone.0172161","article-title":"Liver X receptor agonist treatment significantly affects phenotype and transcriptome of APOE3 and APOE4 Abca1 haplo-deficient mice","volume":"12","year":"2017","journal-title":"PLoS One"},{"key":"2025080117105391000_2025.07.25.666575v1.22","doi-asserted-by":"publisher","DOI":"10.1038\/srep24048"},{"key":"2025080117105391000_2025.07.25.666575v1.23","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1001-15.2015"},{"issue":"8","key":"2025080117105391000_2025.07.25.666575v1.24","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1111\/jnc.15998","article-title":"Bexarotene drives the self-renewing proliferation of adult neural stem cells, promotes neuron-glial fate shift, and regulates late neuronal differentiation","volume":"168","year":"2024","journal-title":"J Neurochem"},{"key":"2025080117105391000_2025.07.25.666575v1.25","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2702"},{"key":"2025080117105391000_2025.07.25.666575v1.26","doi-asserted-by":"publisher","DOI":"10.1016\/J.CELL.2021.04.048"},{"issue":"7","key":"2025080117105391000_2025.07.25.666575v1.27","doi-asserted-by":"crossref","first-page":"112785","DOI":"10.1016\/j.celrep.2023.112785","article-title":"Multi-transcriptomics reveals brain cellular responses to peripheral infection in Alzheimer\u2019s disease model mice","volume":"42","year":"2023","journal-title":"Cell Rep"},{"key":"2025080117105391000_2025.07.25.666575v1.28","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1874-1"},{"key":"2025080117105391000_2025.07.25.666575v1.29","doi-asserted-by":"crossref","unstructured":"Finak G , McDavid A , Yajima M , Deng J , Gersuk V , Shalek AK , et al. MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data. Genome Biol. 2015;16:278.","DOI":"10.1186\/s13059-015-0844-5"},{"key":"2025080117105391000_2025.07.25.666575v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.06.021"},{"key":"2025080117105391000_2025.07.25.666575v1.31","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0695-9"},{"key":"2025080117105391000_2025.07.25.666575v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.03.008"},{"key":"2025080117105391000_2025.07.25.666575v1.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.018"},{"key":"2025080117105391000_2025.07.25.666575v1.34","doi-asserted-by":"publisher","DOI":"10.1093\/NAR\/GKAC194"},{"issue":"3","key":"2025080117105391000_2025.07.25.666575v1.35","first-page":"100141","article-title":"clusterProfiler 4.0: A universal enrichment tool for interpreting omics data","volume":"2","year":"2021","journal-title":"Innovation (Camb)"},{"key":"2025080117105391000_2025.07.25.666575v1.36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0294236"},{"key":"2025080117105391000_2025.07.25.666575v1.37","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9"},{"key":"2025080117105391000_2025.07.25.666575v1.38","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.7400784"},{"key":"2025080117105391000_2025.07.25.666575v1.39","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-0624-8"},{"key":"2025080117105391000_2025.07.25.666575v1.40","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-00783-4"},{"key":"2025080117105391000_2025.07.25.666575v1.41","doi-asserted-by":"crossref","unstructured":"Xu P , Zhai Y , Wang J . The Role of PPAR and Its Cross-Talk with CAR and LXR in Obesity and Atherosclerosis. Int J Mol Sci. 2018;19(4).","DOI":"10.3390\/ijms19041260"},{"key":"2025080117105391000_2025.07.25.666575v1.42","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.109.189506"},{"issue":"1","key":"2025080117105391000_2025.07.25.666575v1.43","first-page":"121","article-title":"Cell-type-specific aging clocks to quantify aging and rejuvenation in neurogenic regions of the brain","volume":"3","year":"2023","journal-title":"Nat Aging"},{"key":"2025080117105391000_2025.07.25.666575v1.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.12.044"},{"key":"2025080117105391000_2025.07.25.666575v1.45","doi-asserted-by":"publisher","DOI":"10.1038\/nm838"},{"key":"2025080117105391000_2025.07.25.666575v1.46","doi-asserted-by":"publisher","DOI":"10.1038\/nm1058"},{"key":"2025080117105391000_2025.07.25.666575v1.47","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14574"},{"key":"2025080117105391000_2025.07.25.666575v1.48","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.05.003"},{"key":"2025080117105391000_2025.07.25.666575v1.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.06.038"},{"key":"2025080117105391000_2025.07.25.666575v1.50","first-page":"5575090","article-title":"Annexin A3 as a Marker Protein for Microglia in the Central Nervous System of Rats","volume":"2021","year":"2021","journal-title":"Neural Plast"},{"issue":"2","key":"2025080117105391000_2025.07.25.666575v1.51","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1161\/STROKEAHA.119.027037","article-title":"Bexarotene Enhances Macrophage Erythrophagocytosis and Hematoma Clearance in Experimental Intracerebral Hemorrhage","volume":"51","year":"2020","journal-title":"Stroke"},{"key":"2025080117105391000_2025.07.25.666575v1.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2024.122867"},{"key":"2025080117105391000_2025.07.25.666575v1.53","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2019.1596488"},{"issue":"1","key":"2025080117105391000_2025.07.25.666575v1.54","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s40035-023-00343-3","article-title":"Inflammasome activation under high cholesterol load triggers a protective microglial phenotype while promoting neuronal pyroptosis","volume":"12","year":"2023","journal-title":"Transl Neurodegener"},{"key":"2025080117105391000_2025.07.25.666575v1.55","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20171265"},{"key":"2025080117105391000_2025.07.25.666575v1.56","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24105"},{"key":"2025080117105391000_2025.07.25.666575v1.57","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-015-9627-8"},{"key":"2025080117105391000_2025.07.25.666575v1.58","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05439-w"},{"key":"2025080117105391000_2025.07.25.666575v1.59","doi-asserted-by":"crossref","first-page":"738991","DOI":"10.3389\/fphys.2021.738991","article-title":"The Lipocalin Apolipoprotein D Functional Portrait: A Systematic Review","volume":"12","year":"2021","journal-title":"Front Physiol"},{"issue":"3","key":"2025080117105391000_2025.07.25.666575v1.60","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1002\/glia.23274","article-title":"Myelin extracellular leaflet compaction requires apolipoprotein D membrane management to optimize lysosomal-dependent recycling and glycocalyx removal","volume":"66","year":"2018","journal-title":"Glia"},{"key":"2025080117105391000_2025.07.25.666575v1.61","doi-asserted-by":"crossref","first-page":"892968","DOI":"10.3389\/fncel.2022.892968","article-title":"Current Insights Into Oligodendrocyte Metabolism and Its Power to Sculpt the Myelin Landscape","volume":"16","year":"2022","journal-title":"Front Cell Neurosci"},{"key":"2025080117105391000_2025.07.25.666575v1.62","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20441"},{"issue":"12","key":"2025080117105391000_2025.07.25.666575v1.63","doi-asserted-by":"crossref","first-page":"9043","DOI":"10.1007\/s12035-018-1041-9","article-title":"Bexarotene Modulates Retinoid-X-Receptor Expression and Is Protective Against Neurotoxic Endoplasmic Reticulum Stress Response and Apoptotic Pathway Activation","volume":"55","year":"2018","journal-title":"Mol Neurobiol"},{"key":"2025080117105391000_2025.07.25.666575v1.64","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2005.09.004"},{"key":"2025080117105391000_2025.07.25.666575v1.65","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-015-1522-0"},{"key":"2025080117105391000_2025.07.25.666575v1.66","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.119.316463"},{"key":"2025080117105391000_2025.07.25.666575v1.67","doi-asserted-by":"crossref","unstructured":"Mojzisch A , Brehm MA . The Manifold Cellular Functions of von Willebrand Factor. Cells. 2021;10(9).","DOI":"10.3390\/cells10092351"},{"key":"2025080117105391000_2025.07.25.666575v1.68","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.06.013"},{"issue":"5","key":"2025080117105391000_2025.07.25.666575v1.69","doi-asserted-by":"crossref","first-page":"100055","DOI":"10.1016\/j.cellin.2022.100055","article-title":"Endothelial RGS12 governs angiogenesis in inflammatory arthritis by controlling cilia formation and elongation via MYCBP2 signaling","volume":"1","year":"2022","journal-title":"Cell Insight"},{"key":"2025080117105391000_2025.07.25.666575v1.70","doi-asserted-by":"publisher","DOI":"10.1172\/JCI33022"},{"key":"2025080117105391000_2025.07.25.666575v1.71","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-012-9255-3"},{"issue":"1","key":"2025080117105391000_2025.07.25.666575v1.72","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s12943-017-0640-9","article-title":"Hsp90\u03b2 promoted endothelial cell-dependent tumor angiogenesis in hepatocellular carcinoma","volume":"16","year":"2017","journal-title":"Mol Cancer"},{"key":"2025080117105391000_2025.07.25.666575v1.73","first-page":"443","article-title":"Pleiotrophin as a central nervous system neuromodulator, evidences from the hippocampus","volume":"8","year":"2014","journal-title":"Front Cell Neurosci"},{"key":"2025080117105391000_2025.07.25.666575v1.74","doi-asserted-by":"crossref","unstructured":"Vidovic N , Spittau B . Microglial Transforming Growth Factor-\u03b2 Signaling in Alzheimer\u2019s Disease. Int J Mol Sci. 2024;25(6).","DOI":"10.3390\/ijms25063090"},{"key":"2025080117105391000_2025.07.25.666575v1.75","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.526095"},{"key":"2025080117105391000_2025.07.25.666575v1.76","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.652008"},{"key":"2025080117105391000_2025.07.25.666575v1.77","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-016-0173-2"},{"key":"2025080117105391000_2025.07.25.666575v1.78","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.600833"},{"issue":"8","key":"2025080117105391000_2025.07.25.666575v1.79","doi-asserted-by":"crossref","first-page":"166841","DOI":"10.1016\/j.bbadis.2023.166841","article-title":"Bezafibrate confers neuroprotection in the 5xFAD mouse model of Alzheimer\u2019s disease","volume":"1869","year":"2023","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"issue":"1","key":"2025080117105391000_2025.07.25.666575v1.80","first-page":"100360","article-title":"Myelin lipid metabolism and its role in myelination and myelin maintenance","volume":"4","year":"2023","journal-title":"Innovation (Camb"},{"key":"2025080117105391000_2025.07.25.666575v1.81","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0726-16.2016"},{"key":"2025080117105391000_2025.07.25.666575v1.82","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2008.42"},{"issue":"2","key":"2025080117105391000_2025.07.25.666575v1.83","first-page":"425","article-title":"Therapeutic effect of exogenous hsp70 in mouse models of Alzheimer\u2019s disease","volume":"38","year":"2014","journal-title":"J Alzheimers Dis"},{"key":"2025080117105391000_2025.07.25.666575v1.84","doi-asserted-by":"crossref","first-page":"100253","DOI":"10.1016\/j.bbih.2021.100253","article-title":"Intranasal HSP70 administration protects against dopaminergic denervation and modulates neuroinflammatory response in the 6-OHDA rat model","volume":"14","year":"2021","journal-title":"Brain Behav Immun Health"},{"key":"2025080117105391000_2025.07.25.666575v1.85","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M048918"},{"key":"2025080117105391000_2025.07.25.666575v1.86","doi-asserted-by":"publisher","DOI":"10.1017\/S000711451100225X"},{"key":"2025080117105391000_2025.07.25.666575v1.87","doi-asserted-by":"publisher","DOI":"10.1242\/dev.152520"},{"issue":"12","key":"2025080117105391000_2025.07.25.666575v1.88","doi-asserted-by":"crossref","first-page":"111842","DOI":"10.1016\/j.celrep.2022.111842","article-title":"SOX2 is essential for astrocyte maturation and its deletion leads to hyperactive behavior in mice","volume":"41","year":"2022","journal-title":"Cell Rep"},{"key":"2025080117105391000_2025.07.25.666575v1.89","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2021.135764"},{"key":"2025080117105391000_2025.07.25.666575v1.90","doi-asserted-by":"crossref","unstructured":"Georgieva I , Tchekalarova J , Iliev D , Tzoneva R . Endothelial Senescence and Its Impact on Angiogenesis in Alzheimer\u2019s Disease. Int J Mol Sci. 2023;24(14).","DOI":"10.3390\/ijms241411344"},{"key":"2025080117105391000_2025.07.25.666575v1.91","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04369-3"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.07.25.666575","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:08:32Z","timestamp":1782277712000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.07.25.666575"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,31]]},"references-count":91,"URL":"https:\/\/doi.org\/10.1101\/2025.07.25.666575","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.3390\/ijms27052435","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2025,7,31]]},"subtype":"preprint"}}