Faulty neuronal determination and cell polarization are reverted by modulating HD early phenotypes
In: Proceedings of the National Academy of Sciences of the United States of America, Jg. 115 (2018-01-23), Heft 4
academicJournal
- e762 - e771
Zugriff:
Increasing evidence suggests that early neurodevelopmental defects in Huntington's disease (HD) patients could contribute to the later adult neurodegenerative phenotype. Here, by using HD-derived induced pluripotent stem cell lines, we report that early telencephalic induction and late neural identity are affected in cortical and striatal populations. We show that a large CAG expansion causes complete failure of the neuro-ectodermal acquisition, while cells carrying shorter CAGs repeats show gross abnormalities in neural rosette formation as well as disrupted cytoarchitecture in cortical organoids. Gene-expression analysis showed that control organoid overlapped with mature human fetal cortical areas, while HD organoids correlated with the immature ventricular zone/subventricular zone. We also report that defects in neuroectoderm and rosette formation could be rescued by molecular and pharmacological approaches leading to a recovery of striatal identity. These results show that mutant huntingtin precludes normal neuronal fate acquisition and highlights a possible connection between mutant huntingtin and abnormal neural development in HD.
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Faulty neuronal determination and cell polarization are reverted by modulating HD early phenotypes
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Autor/in / Beteiligte Person: | Conforti, P ; Besusso, D ; Bocchi, VD ; Faedo, A ; Cesana, E ; Rossetti, G ; Ranzani, V ; Svendsen, CN ; Thompson, LM ; Toselli, M ; Biella, G ; Pagani, M ; Cattaneo, E |
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Zeitschrift: | Proceedings of the National Academy of Sciences of the United States of America, Jg. 115 (2018-01-23), Heft 4 |
Veröffentlichung: | eScholarship, University of California, 2018 |
Medientyp: | academicJournal |
Umfang: | e762 - e771 |
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