PLX075123

GSE109534: Human Huntingtons Disease iPSC-derived cortical neurons display altered transcriptomics, morphology and electrophysiological maturation

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

Huntington's disease (HD) is a neurodegenerative disease caused by an expanded CAG repeat in the Huntingtin (HTT) gene. Induced pluripotent stem cell (iPSC) models of HD provide an opportunity to study the mechanisms underlying disease pathology in patient tissues relevant to disease. Murine studies have demonstrated that HTT is intricately involved in corticogenesis, and mutant (mt) HTT cannot compensate for the loss of non-CAG-expanded HTT. However, the critical effect of mtHTT in human corticogenesis has not yet been specifically explored and due to inherent differences in cortical development and timing between humans and mice. We therefore differentiated HD and non-diseased iPSCs into functional cortical neurons. While HD patient iPSCs can be successfully differentiated towards a cortical fate in culture, the resulting neurons display transcriptomic, morphological and functional phenotypes indicative of altered neurodevelopment. This is the first demonstration of altered corticogenesis from HD human patient cells, further supporting the potential neurodevelopmental aspect of HD. SOURCE: yizhou wang (yizhou.wang@cshs.org) - cedars sinai medical center