Aberrant Development Corrected in Adult-Onset Huntington's Disease iPSC-Derived Neuronal Cultures via WNT Signaling Modulation
Charlene Smith-Geater, Sarah Hernandez, Ryan G. Lim, Miriam Adam, Jie Wu, Jennifer Stocksdale, Brook T. Wassie, Maxwell P. Gold, Keona Q. Wang, Ricardo Miramontes, Lexi Kopan, Iliana Orellana, Shona Joy, Paul J. Kemp, Nicholas D. Allen, Ernest Fraenkel, Leslie M. Thompson
Abstract
neural stem cell (NSC) population is observed selectively in adult-onset HD iPSCs during differentiation. Treatment with a WNT inhibitor abrogates this NSC population while preserving neurons. Taken together, our findings identify a mechanism that may promote aberrant neurodevelopment and adult neurogenesis in adult-onset HD striatal neurons with the potential for therapeutic compensation.
Topics & Concepts
BiologyInduced pluripotent stem cellWnt signaling pathwayHuntington's diseaseTranscriptomeEpigenomicsMechanism (biology)Cell biologyNeuroscienceDiseaseGeneticsSignal transductionEmbryonic stem cellDNA methylationGene expressionGenePathologyMedicinePhilosophyEpistemologyGenetic Neurodegenerative DiseasesPluripotent Stem Cells ResearchRNA Research and Splicing