Journal
STEM CELL REPORTS
Volume 9, Issue 2, Pages 587-599Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2017.06.005
Keywords
-
Categories
Funding
- Monument Trust Discovery Award from Parkinson's UK
- Parkinson's UK [H-1102]
- IMI StemBANCC [115439]
- Innovative Medicines Initiative Joint Undertaking from the European Union's Seventh Framework Program (FP7) [115439]
- Innovative Medicines Initiative Joint Undertaking from EFPIA companies
- Wellcome Trust [WTISSF121302, 090532/Z/09/Z]
- Oxford Martin School [LC0910-004]
- MRC Hub grant [G0900747 91070]
- Medical Research Council (MRC)
- Brains for Dementia Research (BDR) (Alzheimer Society and Alzheimer Research UK)
- Autistica UK
- NIHR Oxford Biomedical Research Center
- MRC [MR/L023784/1, MR/M024962/1, MC_EX_MR/N50192X/1, MR/L022656/1] Funding Source: UKRI
- Alzheimers Research UK [ARUK-ESG2012-9] Funding Source: researchfish
- Medical Research Council [MC_EX_MR/N50192X/1, MR/M024962/1, MR/L023784/1, MR/L022656/1] Funding Source: researchfish
- Parkinson's UK [J-0901, H-1102] Funding Source: researchfish
Ask authors/readers for more resources
The H1 haplotype of the microtubule-associated protein tau (MAPT) locus is genetically associated with neurodegenerative diseases, including Parkinson's disease (PD), and affects gene expression and splicing. However, the functional impact on neurons of such expression differences has yet to be fully elucidated. Here, we employ extended maturation phases during differentiation of induced pluripotent stem cells (iPSCs) into mature dopaminergic neuronal cultures to obtain cultures expressing all six adult tau protein isoforms. After 6 months of maturation, levels of exon 3+ and exon 10+ transcripts approach those of adult brain. Mature dopaminergic neuronal cultures display haplotype differences in expression, with H1 expressing 22% higher levels of MAPT transcripts than H2 and H2 expressing 2-fold greater exon 3+ transcripts than H1. Furthermore, knocking down adult tau protein variants alters axonal transport velocities in mature iPSC-derived dopaminergic neuronal cultures. This work links haplotype-specific MAPT expression with a biologically functional outcome relevant for PD.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available