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Culture variabilities of human iPSC-derived cerebral organoids are a major Issue for the modelling of phenotypes observed in Alzheimer's Disease
Citation
Hernandez, D and Rooney, LA and Daniszewski, M and Gulluyan, L and Liang, HH and Cook, AL and Hewitt, AW and Pebay, A, Culture variabilities of human iPSC-derived cerebral organoids are a major Issue for the modelling of phenotypes observed in Alzheimer's Disease, Stem Cell Reviews and Reports ISSN 2629-3277 (2021) [Refereed Article]
Copyright Statement
Copyright The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021
DOI: doi:10.1007/s12015-021-10147-5
Abstract
Apolipoprotein E (APOE) is the most important susceptibility gene for late onset of Alzheimer’s disease (AD), with the presence
of APOE-ε4 associated with increased risk of developing AD. Here, we reprogrammed human fibroblasts from individuals with
different APOE-ε genotypes into induced pluripotent stem cells (iPSCs), and generated isogenic lines with different APOE
profiles. Following characterisation of the newly established iPSC lines, we used an unguided/unpatterning differentiation
method to generate six-month-old cerebral organoids from all iPSC lines to assess the suitability of this in vitro system to
measure APOE, β amyloid, and Tau phosphorylation levels. We identified variabilities in the organoids’ cell composition
between cell lines, and between batches of differentiation for each cell line. We observed more homogenous cerebral organoids,
and similar levels of APOE, β amyloid, and Tau when using the CRISPR-edited APOE isogenic lines, with the exception of one
site of Tau phosphorylation which was higher in the APOE-ε4/ε4 organoids. These data describe that pathological hallmarks of
AD are observed in cerebral organoids, and that their variation is mainly independent of the APOE-ε status of the cells, but
associated with the high variability of cerebral organoid differentiation. It demonstrates that the cell-line-to-cell-line and batch-to batch variabilities need to be considered when using cerebral organoids.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | cerebral organoid, human induced pluripotent stem cell, APOE, tau, β amyloid, CRISPR/Cas9 |
| Research Division: | Biomedical and Clinical Sciences |
| Research Group: | Neurosciences |
| Research Field: | Neurology and neuromuscular diseases |
| Objective Division: | Expanding Knowledge |
| Objective Group: | Expanding knowledge |
| Objective Field: | Expanding knowledge in the biomedical and clinical sciences |
| UTAS Author: | Cook, AL (Associate Professor Tony Cook) |
| UTAS Author: | Hewitt, AW (Professor Alex Hewitt) |
| ID Code: | 145020 |
| Year Published: | 2021 |
| Web of Science® Times Cited: | 8 |
| Deposited By: | Wicking Dementia Research and Education Centre |
| Deposited On: | 2021-06-24 |
| Last Modified: | 2021-11-01 |
| Downloads: | 0 |
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