Induction of astrocyte reactivity promotes neurodegeneration in human pluripotent stem cell models.
Stem Cell Reports
; 19(8): 1122-1136, 2024 Aug 13.
Article
in En
| MEDLINE
| ID: mdl-39094561
ABSTRACT
Reactive astrocytes are known to exert detrimental effects upon neurons in several neurodegenerative diseases, yet our understanding of how astrocytes promote neurotoxicity remains incomplete, especially in human systems. In this study, we leveraged human pluripotent stem cell (hPSC) models to examine how reactivity alters astrocyte function and mediates neurodegeneration. hPSC-derived astrocytes were induced to a reactive phenotype, at which point they exhibited a hypertrophic profile and increased complement C3 expression. Functionally, reactive astrocytes displayed decreased intracellular calcium, elevated phagocytic capacity, and decreased contribution to the blood-brain barrier. Subsequently, co-culture of reactive astrocytes with a variety of neuronal cell types promoted morphological and functional alterations. Furthermore, when reactivity was induced in astrocytes from patient-specific hPSCs (glaucoma, Alzheimer's disease, and amyotrophic lateral sclerosis), the reactive state exacerbated astrocytic disease-associated phenotypes. These results demonstrate how reactive astrocytes modulate neurodegeneration, significantly contributing to our understanding of a role for reactive astrocytes in neurodegenerative diseases.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Astrocytes
/
Coculture Techniques
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Pluripotent Stem Cells
Limits:
Humans
Language:
En
Journal:
Stem Cell Reports
Year:
2024
Document type:
Article
Affiliation country:
Estados Unidos
Publication country:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
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US
/
USA