Human iPSC-derived Astrocytes Transplanted into the Mouse Brain Display three Morphological Responses to Amyloid-β Plaques
Background: Increasing evidence for a direct contribution of astrocytes to neuroinflammatory and neurodegenerative processes causing Alzheimer’s disease comes from molecular 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.
Methods: To address these challenges, we established an approach to study human astroglia within the context of the mouse brain by transplanting human induced pluripotent stem cell (hiPSC)-derived glia progenitors into neonatal brains of immunodeficient mice.
Results: Xenografted (hiPSC)-derived glia progenitors differentiate into astrocytes that integrate functionally within the mouse host brain and mature in a cell-autonomous way retaining human-specific morphologies, unique features and physiological properties. In Alzheimer´s chimeric brains, transplanted hiPSC-derived astrocytes respond to the presence of amyloid plaques with various morphological changes that seem independent of the APOE allelic background.
Conclusion: In sum, this chimeric model has great potential to analyze the role of patient-derived and genetically modified astroglia in Alzheimer’s disease. Keywords: human induced pluripotent stem cells (hiPSCs), astrocytes, chimeric mouse models, Alzheimer’s disease, amyloid plaques, APOE
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Posted 24 Nov, 2020
On 21 Jan, 2021
Received 20 Jan, 2021
On 11 Jan, 2021
Received 01 Jan, 2021
Received 27 Dec, 2020
On 23 Dec, 2020
On 22 Dec, 2020
Invitations sent on 21 Dec, 2020
On 25 Nov, 2020
On 25 Nov, 2020
On 20 Nov, 2020
On 18 Nov, 2020
Human iPSC-derived Astrocytes Transplanted into the Mouse Brain Display three Morphological Responses to Amyloid-β Plaques
Posted 24 Nov, 2020
On 21 Jan, 2021
Received 20 Jan, 2021
On 11 Jan, 2021
Received 01 Jan, 2021
Received 27 Dec, 2020
On 23 Dec, 2020
On 22 Dec, 2020
Invitations sent on 21 Dec, 2020
On 25 Nov, 2020
On 25 Nov, 2020
On 20 Nov, 2020
On 18 Nov, 2020
Background: Increasing evidence for a direct contribution of astrocytes to neuroinflammatory and neurodegenerative processes causing Alzheimer’s disease comes from molecular 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.
Methods: To address these challenges, we established an approach to study human astroglia within the context of the mouse brain by transplanting human induced pluripotent stem cell (hiPSC)-derived glia progenitors into neonatal brains of immunodeficient mice.
Results: Xenografted (hiPSC)-derived glia progenitors differentiate into astrocytes that integrate functionally within the mouse host brain and mature in a cell-autonomous way retaining human-specific morphologies, unique features and physiological properties. In Alzheimer´s chimeric brains, transplanted hiPSC-derived astrocytes respond to the presence of amyloid plaques with various morphological changes that seem independent of the APOE allelic background.
Conclusion: In sum, this chimeric model has great potential to analyze the role of patient-derived and genetically modified astroglia in Alzheimer’s disease. Keywords: human induced pluripotent stem cells (hiPSCs), astrocytes, chimeric mouse models, Alzheimer’s disease, amyloid plaques, APOE
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Due to technical limitations, full-text HTML conversion of this manuscript could not be completed. However, the manuscript can be downloaded and accessed as a PDF.