{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T12:45:05Z","timestamp":1787661905370,"version":"build-2736575974"},"reference-count":58,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T00:00:00Z","timestamp":1693353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["R01 NS045585"],"award-info":[{"award-number":["R01 NS045585"]}]},{"name":"National Institute of Health","award":["R01 NS129502"],"award-info":[{"award-number":["R01 NS129502"]}]},{"name":"National Institute of Health","award":["R01 NS107262"],"award-info":[{"award-number":["R01 NS107262"]}]},{"name":"National Institute of Health","award":["R01 NS082308"],"award-info":[{"award-number":["R01 NS082308"]}]},{"name":"National Institute of Health","award":["17\/FRL\/4860"],"award-info":[{"award-number":["17\/FRL\/4860"]}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["R01 NS045585"],"award-info":[{"award-number":["R01 NS045585"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["R01 NS129502"],"award-info":[{"award-number":["R01 NS129502"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["R01 NS107262"],"award-info":[{"award-number":["R01 NS107262"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["R01 NS082308"],"award-info":[{"award-number":["R01 NS082308"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["17\/FRL\/4860"],"award-info":[{"award-number":["17\/FRL\/4860"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The transformation of astrocytes into reactive states constitutes a biological response of the central nervous system under a variety of pathological insults. Astrocytes display diverse homeostatic identities that are developmentally predetermined and regionally specified. Upon transformation into reactive states associated with neurodegenerative diseases and other neurological disorders, astrocytes acquire diverse reactive phenotypes. However, it is not clear whether their reactive phenotypes are dictated by region-specific homeostatic identity or by the nature of an insult. To address this question, region-specific gene expression profiling was performed for four brain regions (cortex, hippocampus, thalamus, and hypothalamus) in mice using a custom NanoString panel consisting of selected sets of genes associated with astrocyte functions and their reactivity for five conditions: prion disease, traumatic brain injury, brain ischemia, 5XFAD Alzheimer\u2019s disease model and normal aging. Upon transformation into reactive states, genes that are predominantly associated with astrocytes were found to respond to insults in a region-specific manner. Regardless of the nature of the insult or the insult-specificity of astrocyte response, strong correlations between undirected GSA (gene set analysis) scores reporting on astrocyte reactivity and on their homeostatic functions were observed within each individual brain region. The insult-specific gene expression signatures did not separate well from each other and instead partially overlapped, forming continuums. The current study demonstrates that region-specific homeostatic identities of astrocytes are important for defining their response to pathological insults. Within region-specific populations, reactive astrocytes show continuums of gene expression signatures, partially overlapping between individual insults.<\/jats:p>","DOI":"10.3390\/cells12172172","type":"journal-article","created":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T09:48:15Z","timestamp":1693388895000},"page":"2172","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Region-Specific Homeostatic Identity of Astrocytes Is Essential for Defining Their Response to Pathological Insults"],"prefix":"10.3390","volume":"12","author":[{"given":"Natallia","family":"Makarava","sequence":"first","affiliation":[{"name":"Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"},{"name":"Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Mychko","sequence":"additional","affiliation":[{"name":"Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"},{"name":"Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara","family":"Molesworth","sequence":"additional","affiliation":[{"name":"Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"},{"name":"Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer Chen-Yu","family":"Chang","sequence":"additional","affiliation":[{"name":"Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"},{"name":"Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca J.","family":"Henry","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Shock, Trauma and Anesthesiology Research (STAR) Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalya","family":"Tsymbalyuk","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volodymyr","family":"Gerzanich","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5373-1988","authenticated-orcid":false,"given":"J. 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