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Research article
Amaia M Arranz
Achucarro
Corresponding Author
ORCiD: https://orcid.org/0000-0002-8314-7870
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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
Keywords
human induced pluripotent stem cells (hiPSCs), astrocytes, chimeric mouse models, Alzheimer’s disease, amyloid plaques, APOE
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Peer Review Timeline
CURRENT STATUS: Under Revision
Version 1
Posted 24 Nov, 2020
No community comments so far
Editorial decision: Major revision
On 21 Jan, 2021
Review #3 received
Received 20 Jan, 2021
Reviewer #3 agreed
On 11 Jan, 2021
Review #2 received
Received 01 Jan, 2021
Review #1 received
Received 27 Dec, 2020
Reviewer #2 agreed
On 23 Dec, 2020
Reviewer #1 agreed
On 22 Dec, 2020
Reviewers invited
Invitations sent on 21 Dec, 2020
Editor assigned
On 25 Nov, 2020
Editor invited
On 25 Nov, 2020
Submission checks complete
On 20 Nov, 2020
First submitted
On 18 Nov, 2020
Metrics
Comments: 0
PDF Downloads: ...
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Subject Areas
Cellular & Molecular Neuroscience
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This preprint is under consideration at Molecular Neurodegeneration. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Amaia M Arranz
Achucarro
Corresponding Author
ORCiD: https://orcid.org/0000-0002-8314-7870
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Revision
Version 1
Posted 24 Nov, 2020
No community comments so far
Editorial decision: Major revision
On 21 Jan, 2021
Review #3 received
Received 20 Jan, 2021
Reviewer #3 agreed
On 11 Jan, 2021
Review #2 received
Received 01 Jan, 2021
Review #1 received
Received 27 Dec, 2020
Reviewer #2 agreed
On 23 Dec, 2020
Reviewer #1 agreed
On 22 Dec, 2020
Reviewers invited
Invitations sent on 21 Dec, 2020
Editor assigned
On 25 Nov, 2020
Editor invited
On 25 Nov, 2020
Submission checks complete
On 20 Nov, 2020
First submitted
On 18 Nov, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cellular & Molecular Neuroscience
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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
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