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Human stem cell-derived neurons: a system to study human tau function and dysfunction.

TitleHuman stem cell-derived neurons: a system to study human tau function and dysfunction.
Publication TypeJournal Article
Year of Publication2010
AuthorsIovino M, Patani R, Watts C, Chandran S, Spillantini MGrazia
JournalPLoS One
Date Published2010
KeywordsAdult, Blotting, Western, Brain, Cell Line, Cells, Cultured, Embryonic Stem Cells, Fetal Stem Cells, Fluorescent Antibody Technique, Gene Expression, Humans, Neurons, Peptide Fragments, Phosphorylation, Protein Isoforms, Reverse Transcriptase Polymerase Chain Reaction, tau Proteins, Transfection

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.

Alternate JournalPLoS ONE
PubMed ID21085657
PubMed Central IDPMC2978712
Grant ListG0800784 / / Medical Research Council / United Kingdom
/ / Wellcome Trust / United Kingdom