title: Human stem cell-derived neurons: a system to study human tau function and dysfunction.
abstract: 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.
  
  
  RESULTS
  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.
authors.affiliation: Department of Clinical Neurosciences, Cambridge Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Iovino
authors.forename: Rickie
authors.initials: R
authors.lastname: Patani
authors.forename: Colin
authors.initials: C
authors.lastname: Watts
authors.forename: Siddharthan
authors.initials: S
authors.lastname: Chandran
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Spillantini
mesh_terms: D000328:Adult; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D053686:Fetal Stem Cells / Q000166:cytology / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics / Q000502:physiology; D010766:Phosphorylation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
chemical_list: C054369:MAPT protein, human; D010446:Peptide Fragments; D020033:Protein Isoforms; D016875:tau Proteins