Human stem cell-derived neurons: a system to study human tau function and dysfunction
Open accessAbstract
BACKGROUND: Intracellular filamentous deposits containing microtubule-associated protein tau constitute a defining characteristic of many neurodegenerative disorders. Current experimental models to study tau pathology in vitro do not usually recapitulate the tau expression pattern characteristic of adult human brain. In this study, we have investigated whether human embryonic stem cell-derived neurons could be a good model to study human tau distribution, function and dysfunction. METHODOLOGY/PRINCIPAL FINDINGS: Using RT-PCR, immunohistochemistry, western blotting and cell transfections we have investigated whether all 6 adult human brain tau isoforms are expressed in neurons derived from human embryonic and fetal stem cells and whether 4 repeat tau over-expression alone, or with the F3 tau repeat fragment, (amino acid 258-380 of the 2N4R tau isoform with the ΔK280 mutation) affects tau distribution. We found that the shortest 3 repeat tau isoform, similarly to human brain, is the first to be expressed during neuronal differentiation while the other 5 tau isoforms are expressed later. Over expression of tau with 4 repeats affects tau cellular distribution and the short tau F3 fragment appears to increase tau phosphorylation but this effect does not appear to be toxic for the cell. CONCLUSIONS: Our results indicate that human embryonic stem cell-derived neurons express all 6 tau isoforms and are a good model in which to study tau physiology and pathology.
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iPSC-derived neurons at DIV 7-8 predominantly express 3R tau, with 4R tau expression increasing during maturation.
“iPSC-derived neurons at DIV 7–8 predominantly express 3R tau, with 4R tau expression increasing during maturation”
From Tau hyperphosphorylation impairs cooperative binding to microtubules and perturbs organelle trafficking in neurons (2026) · cites this paper as Iovino et al., 2010
The Results and Discussion (page not available in our copy) report that 3R tau appears early and 4R tau increases with maturation. But the studied neurons were derived from human embryonic or fetal stem cells, not iPSCs; the paper therefore does not establish the claimed pattern in iPSC-derived neurons at DIV 7–8. (LLM, conf=0.88)
Experimental — accuracy not yet measuredDIV7-8 iPSC-derived neurons predominantly express 3R tau, whereas our rescue experiments used 4R0N tau.
“DIV7–8 iPSC-derived neurons predominantly express 3R tau (Iovino et al., 2010; Iovino et al., 2015; Sposito et al., 2015), whereas our rescue experiments used 4R0N tau”
From Tau hyperphosphorylation impairs cooperative binding to microtubules and perturbs organelle trafficking in neurons (2026) · cites this paper as Iovino et al., 2010
The Results section, “Adult human brain tau isoforms are expressed in hESC-derived neurons” (page unavailable), reports 3R tau mRNA at 7 DIV, with 4R tau appearing later. But the study used embryonic stem cell-derived neurons, not iPSC-derived neurons, and detected 3R tau protein only from 14 DIV; it does not establish predominant 3R tau protein expression at DIV7–8 in iPSC-derived neurons. The statement about the citing authors’ rescue experiments is their own, not a finding attributed to this source. (LLM, conf=0.86)
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Beaudet, D., Berger, C. L., & Hendricks, A. G. (2026) · eLife · doi:10.7554/elife.110011
- Authors
- Iovino, M., Patani, R., Watts, C., Chandran, S., & Spillantini, M. G.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Spillantini, Maria Grazia
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-11-11
- Volume
- 5
- Issue
- 11
- Pages
- e13947
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2978712
- OpenAlex
- W2088391855
- Cited by
- 40
- References
- 1
- Citations by year
- 2026: 6 · 2024: 3 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 6 · 2014: 3 · 2013: 4 · 2012: 4
- FWCI
- 1.83
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UCL Discovery (University College London) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- Funders
- Wellcome Trust
- Alzheimer's Research Trust
- National Institute for Health and Care Research
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- tau protein, tau isoforms, human embryonic stem cell-derived neurons, fetal stem cells, neuronal differentiation, tau phosphorylation, neurodegenerative disease models, tauopathy
- MeSH terms
- Adult, Brain, Cell Line, Cells, Cultured, Fluorescent Antibody Technique, Humans, Neurons, Peptide Fragments, Phosphorylation, Transfection, Blotting, Western, Gene Expression, tau Proteins, Protein Isoforms, Reverse Transcriptase Polymerase Chain Reaction, Embryonic Stem Cells, Fetal Stem Cells
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