Human iPSC-derived astrocytes transplanted into the mouse brain undergo morphological changes in response to amyloid-β plaques
Authors list
Pranav Preman Julia TCW Sara Calafate An Snellinx Maria Alfonso-Triguero Nikky Corthout Sebastian Munck Dietmar Rudolf Thal Alison M Goate Bart De Strooper Amaia M ArranzAbstract
Background
Increasing 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.
Results
To 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 the APOE allelic background.
Conclusions
In 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.
Journal details
Journal Molecular Neurodegeneration
Volume 16
Issue number 1
Pages 68
Available online
Publication date
Full text links
Publisher website (DOI) 10.1186/s13024-021-00487-8
Europe PubMed Central 34563212
Pubmed 34563212
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