Jess Kelly: From Skin to Synapse: Creating Brain Organoids to Model Huntington's Disease

Three-dimensional (3D) neural organoids are valuable tools for disease modelling. However, current protocols are lengthy and have limited applicability to diseases of aging due to the cells undergoing DNA rejuvenation. Direct-to-induced neural precursor (iNP) cell reprogramming converts human fibroblasts into region-specific neural precursor cells and allows the maintenance of aging factors. This study demonstrates for the first time the ability to generate organoids from directly reprogrammed iNPs from healthy and Huntington’s Disease donors, with region specific neuronal differentiation and disease phenotypes by Day 14 of differentiation. The reduced time required to generate organoids from iNPs, and the ability for direct-to-iNP reprogramming to maintain epigenetic and aging signatures advances current organoid methods and will facilitate future modelling of neurological diseases of aging.