| Autor: |
Joel E. Beevers, Mang Ching Lai, Emma Collins, Heather D.E. Booth, Federico Zambon, Laura Parkkinen, Jane Vowles, Sally A. Cowley, Richard Wade-Martins, Tara M. Caffrey |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
|
| Zdroj: |
Stem Cell Reports, Vol 9, Iss 2, Pp 587-599 (2017) |
| Druh dokumentu: |
article |
| ISSN: |
2213-6711 |
| DOI: |
10.1016/j.stemcr.2017.06.005 |
| Popis: |
Summary: 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. : In this article, Caffrey, Wade-Martins, and colleagues show extended maturation of dopaminergic neuronal cultures gives expression of six adult tau isoforms displaying MAPT haplotype-specific differences in expression. Further, knocking down adult tau protein variants alters axonal transport velocities in mature iPSC-derived dopaminergic neuronal cultures, linking haplotype-specific MAPT expression with a biologically functional outcome relevant for PD. Keywords: MAPT, tau, dopamine neurons, Parkinson's disease, iPSC |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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