Human iPSC-derived astrocytes transplanted into the mouse brain undergo morphological changes in response to amyloid-β plaques

Autor: Julia Tcw, Amaia M. Arranz, Dietmar Rudolf Thal, Bart De Strooper, Pranav Preman, Nikky Corthout, Sara Calafate, An Snellinx, Alison Goate, Maria Alfonso-Triguero, Sebastian Munck
Rok vydání: 2021
Předmět:
Apolipoprotein E
Plaque
Amyloid
Amyloid plaques
DISEASE
ACTIVATION
Mice
0302 clinical medicine
Gene expression
PLASTICITY
Induced pluripotent stem cell
NEURONS
0303 health sciences
Brain
Alzheimer's disease
Genetically modified organism
DIFFERENTIATION
medicine.anatomical_structure
Alzheimer’s disease
Life Sciences & Biomedicine
Astrocyte
Chimeric mouse models
Induced Pluripotent Stem Cells
Context (language use)
Biology
Apolipoprotein E (APOE)
03 medical and health sciences
Cellular and Molecular Neuroscience
Alzheimer Disease
medicine
Animals
Humans
Progenitor cell
RC346-429
Molecular Biology
Human induced pluripotent stem cells (hiPSCs)
030304 developmental biology
Amyloid beta-Peptides
Science & Technology
Methodology
RC952-954.6
Neurosciences
Molecular medicine
GLIAL PROGENITOR CELLS
PATHOLOGY
MICE
Geriatrics
Astrocytes
Neurology. Diseases of the nervous system
Neurosciences & Neurology
Neurology (clinical)
Neuroscience
030217 neurology & neurosurgery
Zdroj: Molecular Neurodegeneration, Vol 16, Iss 1, Pp 1-18 (2021)
Molecular Neurodegeneration
ISSN: 1750-1326
Popis: BackgroundIncreasing evidence for a direct contribution of astrocytes to neuroinflammatory and neurodegenerative processes causing Alzheimer’s disease comes from molecular and functional studies in rodent models. However, these models may not fully recapitulate human disease as human and rodent astrocytes differ considerably in morphology, functionality, and gene expression.ResultsTo address these challenges, we established an approach to study human astrocytes within the mouse brain by transplanting human induced pluripotent stem cell (hiPSC)-derived astrocyte progenitors into neonatal brains. Xenografted hiPSC-derived astrocyte progenitors differentiated into astrocytes that integrated functionally within the mouse host brain and matured in a cell-autonomous way retaining human-specific morphologies, unique features, and physiological properties. In Alzheimer´s chimeric brains, transplanted hiPSC-derived astrocytes responded to the presence of amyloid plaques undergoing morphological changes that seemed independent of theAPOEallelic background.ConclusionsIn sum, we describe here a promising approach that consist of transplanting patient-derived and genetically modified astrocytes into the mouse brain to study human astrocyte pathophysiology in the context of Alzheimer´s disease.
Databáze: OpenAIRE
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