Gatto, N., Dos Santos Souza, C., Shaw, A.C. et al. (12 more authors) (2021) Directly converted astrocytes retain the ageing features of the donor fibroblasts and elucidate the astrocytic contribution to human CNS health and disease. Aging Cell, 20 (1). e13281. ISSN 1474-9718
Abstract
Astrocytes are highly specialised cells, responsible for CNS homeostasis and neuronal activity. Lack of human in vitro systems able to recapitulate the functional changes affecting astrocytes during ageing represents a major limitation to studying mechanisms and potential therapies aiming to preserve neuronal health. Here, we show that induced astrocytes from fibroblasts donors in their childhood or adulthood display age‐related transcriptional differences and functionally diverge in a spectrum of age‐associated features, such as altered nuclear compartmentalisation, nucleocytoplasmic shuttling properties, oxidative stress response and DNA damage response. Remarkably, we also show an age‐related differential response of induced neural progenitor cells derived astrocytes (iNPC‐As) in their ability to support neurons in co‐culture upon pro‐inflammatory stimuli. These results show that iNPC‐As are a renewable, readily available resource of human glia that retain the age‐related features of the donor fibroblasts, making them a unique and valuable model to interrogate human astrocyte function over time in human CNS health and disease.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/4.0/) which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | ageing; astrocytes; direct reprogramming; in vitro model; neurodegeneration; neuroinflammation; neuron‐astrocyte crosstalk; nuclear abnormalities; nucleocytoplasmic transport; oxidative stress |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL BB/S005277/1 Medical Research Council 2114458 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 16 Dec 2020 15:33 |
Last Modified: | 01 Feb 2022 11:24 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1111/acel.13281 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:169095 |
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