Mutual interaction of neurons and astrocytes derived from iPSCs with APP V717L mutation developed the astrocytic phenotypes of Alzheimer's disease.
Alzheimer’s disease
Astrocytes
Co-culture model
Induced pluripotent stem cells (iPSCs)
Neurons
Tripartite synapse
Journal
Inflammation and regeneration
ISSN: 1880-9693
Titre abrégé: Inflamm Regen
Pays: England
ID NLM: 101479577
Informations de publication
Date de publication:
28 Feb 2024
28 Feb 2024
Historique:
received:
05
09
2023
accepted:
22
11
2023
medline:
29
2
2024
pubmed:
29
2
2024
entrez:
28
2
2024
Statut:
epublish
Résumé
The development of induced pluripotent stem cells (iPSCs) technology has enabled human cellular disease modeling for inaccessible cell types, such as neural cells in the brain. However, many of the iPSC-derived disease models established to date typically involve only a single cell type. These monoculture models are inadequate for accurately simulating the brain environment, where multiple cell types interact. The limited cell type diversity in monoculture models hinders the accurate recapitulation of disease phenotypes resulting from interactions between different cell types. Therefore, our goal was to create cell models that include multiple interacting cell types to better recapitulate disease phenotypes. To establish a co-culture model of neurons and astrocytes, we individually induced neurons and astrocytes from the same iPSCs using our novel differentiation methods, and then co-cultured them. We evaluated the effects of co-culture on neurons and astrocytes using immunocytochemistry, immuno-electron microscopy, and Ca The co-culture of the neurons and astrocytes increased the branching of astrocyte processes, the number of GFAP-positive cells, neuronal activities, the number of synapses, and the density of presynaptic vesicles. In addition, immuno-electron microscopy confirmed the formation of a tripartite synaptic structure in the co-culture model, and inhibition of glutamate transporters increased neuronal activity. Compared to the co-culture model of the control iPSCs, the co-culture model of familial AD developed astrogliosis-like phenotype, which was not observed in the monoculture model of astrocytes. Co-culture of iPSC-derived neurons and astrocytes enhanced the morphological changes mimicking the in vivo condition of both cell types. The formation of the functional tripartite synaptic structures in the co-culture model suggested the mutual interaction between the cells. Furthermore, the co-culture model with the APP
Sections du résumé
BACKGROUND
BACKGROUND
The development of induced pluripotent stem cells (iPSCs) technology has enabled human cellular disease modeling for inaccessible cell types, such as neural cells in the brain. However, many of the iPSC-derived disease models established to date typically involve only a single cell type. These monoculture models are inadequate for accurately simulating the brain environment, where multiple cell types interact. The limited cell type diversity in monoculture models hinders the accurate recapitulation of disease phenotypes resulting from interactions between different cell types. Therefore, our goal was to create cell models that include multiple interacting cell types to better recapitulate disease phenotypes.
METHODS
METHODS
To establish a co-culture model of neurons and astrocytes, we individually induced neurons and astrocytes from the same iPSCs using our novel differentiation methods, and then co-cultured them. We evaluated the effects of co-culture on neurons and astrocytes using immunocytochemistry, immuno-electron microscopy, and Ca
RESULTS
RESULTS
The co-culture of the neurons and astrocytes increased the branching of astrocyte processes, the number of GFAP-positive cells, neuronal activities, the number of synapses, and the density of presynaptic vesicles. In addition, immuno-electron microscopy confirmed the formation of a tripartite synaptic structure in the co-culture model, and inhibition of glutamate transporters increased neuronal activity. Compared to the co-culture model of the control iPSCs, the co-culture model of familial AD developed astrogliosis-like phenotype, which was not observed in the monoculture model of astrocytes.
CONCLUSIONS
CONCLUSIONS
Co-culture of iPSC-derived neurons and astrocytes enhanced the morphological changes mimicking the in vivo condition of both cell types. The formation of the functional tripartite synaptic structures in the co-culture model suggested the mutual interaction between the cells. Furthermore, the co-culture model with the APP
Identifiants
pubmed: 38419091
doi: 10.1186/s41232-023-00310-5
pii: 10.1186/s41232-023-00310-5
doi:
Types de publication
Journal Article
Langues
eng
Pagination
8Subventions
Organisme : Grants-in-Aid for Scientific Research (KAKENHI)
ID : #21J21244
Organisme : Grants-in-Aid for Scientific Research (KAKENHI)
ID : #22J11065
Organisme : Grants-in-Aid for Scientific Research (KAKENHI)
ID : #21H02450
Organisme : Grants-in-Aid for Scientific Research (KAKENHI)
ID : #23K18116
Organisme : Grants-in-Aid for Scientific Research (KAKENHI)
ID : #21K06376
Organisme : the Japan Agency for Medical Research and Development (AMED)
ID : JP21bm0804003
Organisme : the Japan Agency for Medical Research and Development (AMED)
ID : JP21bm0804003
Organisme : Cyclic Innovation for Clinical Empowerment
ID : JP17pc0101006
Organisme : Cyclic Innovation for Clinical Empowerment
ID : JP17pc0101006
Organisme : Research and Development Grants for Dementia
ID : 22dk0207060
Informations de copyright
© 2024. The Author(s).
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