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Region-Specific Homeostatic Identity of Astrocytes Is Essential for Defining Their Response to Pathological Insults

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 r...

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Autores principales: Makarava, Natallia, Mychko, Olga, Molesworth, Kara, Chang, Jennifer Chen-Yu, Henry, Rebecca J., Tsymbalyuk, Natalya, Gerzanich, Volodymyr, Simard, J. Marc, Loane, David J., Baskakov, Ilia V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10486627/
https://www.ncbi.nlm.nih.gov/pubmed/37681904
http://dx.doi.org/10.3390/cells12172172
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author Makarava, Natallia
Mychko, Olga
Molesworth, Kara
Chang, Jennifer Chen-Yu
Henry, Rebecca J.
Tsymbalyuk, Natalya
Gerzanich, Volodymyr
Simard, J. Marc
Loane, David J.
Baskakov, Ilia V.
author_facet Makarava, Natallia
Mychko, Olga
Molesworth, Kara
Chang, Jennifer Chen-Yu
Henry, Rebecca J.
Tsymbalyuk, Natalya
Gerzanich, Volodymyr
Simard, J. Marc
Loane, David J.
Baskakov, Ilia V.
author_sort Makarava, Natallia
collection PubMed
description 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’s 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.
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spelling pubmed-104866272023-09-09 Region-Specific Homeostatic Identity of Astrocytes Is Essential for Defining Their Response to Pathological Insults Makarava, Natallia Mychko, Olga Molesworth, Kara Chang, Jennifer Chen-Yu Henry, Rebecca J. Tsymbalyuk, Natalya Gerzanich, Volodymyr Simard, J. Marc Loane, David J. Baskakov, Ilia V. Cells Article 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’s 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. MDPI 2023-08-30 /pmc/articles/PMC10486627/ /pubmed/37681904 http://dx.doi.org/10.3390/cells12172172 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Makarava, Natallia
Mychko, Olga
Molesworth, Kara
Chang, Jennifer Chen-Yu
Henry, Rebecca J.
Tsymbalyuk, Natalya
Gerzanich, Volodymyr
Simard, J. Marc
Loane, David J.
Baskakov, Ilia V.
Region-Specific Homeostatic Identity of Astrocytes Is Essential for Defining Their Response to Pathological Insults
title Region-Specific Homeostatic Identity of Astrocytes Is Essential for Defining Their Response to Pathological Insults
title_full Region-Specific Homeostatic Identity of Astrocytes Is Essential for Defining Their Response to Pathological Insults
title_fullStr Region-Specific Homeostatic Identity of Astrocytes Is Essential for Defining Their Response to Pathological Insults
title_full_unstemmed Region-Specific Homeostatic Identity of Astrocytes Is Essential for Defining Their Response to Pathological Insults
title_short Region-Specific Homeostatic Identity of Astrocytes Is Essential for Defining Their Response to Pathological Insults
title_sort region-specific homeostatic identity of astrocytes is essential for defining their response to pathological insults
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10486627/
https://www.ncbi.nlm.nih.gov/pubmed/37681904
http://dx.doi.org/10.3390/cells12172172
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