Evidence map›Paper›PMID 33725267›Full record

ArticleStem cell reviews and reports2022

Culture Variabilities of Human iPSC-Derived Cerebral Organoids Are a Major Issue for the Modelling of Phenotypes Observed in Alzheimer's Disease.

Damián Hernández, Louise A Rooney, Maciej Daniszewski, Lerna Gulluyan, Helena H Liang, Anthony L Cook, Alex W Hewitt, Alice Pébay

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In one paragraph

Article in Stem cell reviews and reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed, 1 pooled it
4.7field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

50 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Damián HernándezDepartment of Anatomy and Physiology, The University of Melbourne, Parkville, Australia. damian.hernandez@unimelb.edu.au.
Louise A RooneyDepartment of Anatomy and Physiology, The University of Melbourne, Parkville, Australia.
Maciej DaniszewskiDepartment of Anatomy and Physiology, The University of Melbourne, Parkville, Australia.
Lerna GulluyanDepartment of Anatomy and Physiology, The University of Melbourne, Parkville, Australia.
Helena H LiangCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia.
Anthony L CookWicking Dementia Research and Education Centre, University of Tasmania, Hobart, Australia.
Alex W HewittCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia.
Alice PébayDepartment of Anatomy and Physiology, The University of Melbourne, Parkville, Australia. apebay@unimelb.edu.au.ORCID 0000-0002-7408-9453
The Royal Melbourne Hospital · AUUniversity of Tasmania · AUCentre for Eye Research Australia · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Alzheimer DiseaseInduced Pluripotent Stem CellsAmyloid beta-PeptidesApolipoprotein E4Apolipoproteins EHumansOrganoidsPhenotypeAmyloid beta-PeptidesApolipoprotein E4Apolipoproteins EAPOECerebral organoidCRISPR/Cas9Human induced pluripotent stem cellTauβ amyloid

Identifiers

PMID33725267
OpenAlexW3138828571

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.