Human iPSC-derived astrocytes transplanted into the mouse brain undergo morphological changes in response to amyloid-β plaques
Abstract 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 r...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-09-01
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| Series: | Molecular Neurodegeneration |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13024-021-00487-8 |
| _version_ | 1830177008591568896 |
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| author | 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 Arranz |
| author_facet | 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 Arranz |
| author_sort | Pranav Preman |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-17T19:16:43Z |
| format | Article |
| id | doaj.art-6f6aad58ba3e4327a615115ca66accb3 |
| institution | Directory Open Access Journal |
| issn | 1750-1326 |
| language | English |
| last_indexed | 2024-12-17T19:16:43Z |
| publishDate | 2021-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Neurodegeneration |
| spelling | doaj.art-6f6aad58ba3e4327a615115ca66accb32022-12-21T21:35:44ZengBMCMolecular Neurodegeneration1750-13262021-09-0116111810.1186/s13024-021-00487-8Human iPSC-derived astrocytes transplanted into the mouse brain undergo morphological changes in response to amyloid-β plaquesPranav Preman0Julia TCW1Sara Calafate2An Snellinx3Maria Alfonso-Triguero4Nikky Corthout5Sebastian Munck6Dietmar Rudolf Thal7Alison M Goate8Bart De Strooper9Amaia M Arranz10VIB Center for Brain & Disease ResearchDepartment of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount SinaiVIB Center for Brain & Disease ResearchVIB Center for Brain & Disease ResearchAchucarro Basque Center for NeuroscienceVIB Center for Brain & Disease ResearchVIB Center for Brain & Disease ResearchLaboratory for Neuropathology, Department of Imaging and Pathology, Leuven Brain Institute (LBI), Department of Pathology, KU Leuven (University of Leuven), University Hospital LeuvenDepartment of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount SinaiVIB Center for Brain & Disease ResearchVIB Center for Brain & Disease ResearchAbstract 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.https://doi.org/10.1186/s13024-021-00487-8Human induced pluripotent stem cells (hiPSCs)AstrocytesChimeric mouse modelsAlzheimer’s diseaseAmyloid plaquesApolipoprotein E (APOE) |
| spellingShingle | 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 Arranz Human iPSC-derived astrocytes transplanted into the mouse brain undergo morphological changes in response to amyloid-β plaques Molecular Neurodegeneration Human induced pluripotent stem cells (hiPSCs) Astrocytes Chimeric mouse models Alzheimer’s disease Amyloid plaques Apolipoprotein E (APOE) |
| title | Human iPSC-derived astrocytes transplanted into the mouse brain undergo morphological changes in response to amyloid-β plaques |
| title_full | Human iPSC-derived astrocytes transplanted into the mouse brain undergo morphological changes in response to amyloid-β plaques |
| title_fullStr | Human iPSC-derived astrocytes transplanted into the mouse brain undergo morphological changes in response to amyloid-β plaques |
| title_full_unstemmed | Human iPSC-derived astrocytes transplanted into the mouse brain undergo morphological changes in response to amyloid-β plaques |
| title_short | Human iPSC-derived astrocytes transplanted into the mouse brain undergo morphological changes in response to amyloid-β plaques |
| title_sort | human ipsc derived astrocytes transplanted into the mouse brain undergo morphological changes in response to amyloid β plaques |
| topic | Human induced pluripotent stem cells (hiPSCs) Astrocytes Chimeric mouse models Alzheimer’s disease Amyloid plaques Apolipoprotein E (APOE) |
| url | https://doi.org/10.1186/s13024-021-00487-8 |
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