| Autor: |
Watson, LM, Smith, DC, Raimondo, JV, Burman, RJ, Ballo, R, Scholefield, J, Tyers, L, Cowley, SA, Wood, MJA, Kidson, SH, Greenberg, LJ |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| DOI: |
10.1101/288480 |
| Popis: |
Spinocerebellar ataxia type 7 (SCA7) is an inherited neurodegenerative disease that is characterised by ataxia and visual loss. It results from a degeneration of cerebellar Purkinje neurons and retinal photoreceptors caused by a polyglutamine repeat expansion in the ATXN7 gene, a component of the STAGA transcription co-activator complex. As with many neurodegenerative diseases, studies of pathogenesis have been hindered by a lack of disease-relevant models. To this end, we have generated the first induced pluripotent stem cells (iPSCs) from South African SCA7 patients, where the disease occurs at an unusually high frequency as a result of a founder effect. These iPSCs were capable of differentiation into neural and retinal cells, and showed evidence of a transcriptional phenotype affecting components of STAGA ( ATXN7 and KAT2A ) and the heat shock protein pathway ( DNAJA1 and HSP70 ). Functionally, SCA7 iPSC-derived neurons exhibited more negative resting membrane potentials and increased input resistance compared to controls, suggesting reduced excitability in response to synaptic input. These results provide the first evidence of a disease phenotype in SCA7 iPSC-derived cells, establishing a valuable model for the study of neurodegenerative disease s and the development of population-specific therapies. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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