Developing a 3D Human Organoid Model for Cri-du-chat Syndrome

Cri-du-chat syndrome (CdCs), or 5p- syndrome, is a rare genetic disorder with a lack of targeted treatments due to poorly understood underlying cellular mechanisms. To address this, my project aims to develop a physiologically relevant 3D human brain model to study the disease in vitro. I will generate cerebral organoids from patient-derived induced pluripotent stem cells (iPSCs) harboring the characteristic genetic deletion. The model will be rigorously validated by characterizing cellular identities and confirming the preservation of the 5p- deletion. Additionally, disease iNPCs and ultimately neurons will be generated to conduct electrophysiology and bulk RNA and miRNA sequencing. This project will establish a validated human organoid and neuronal model, providing an essential, translational platform for investigating the cellular pathogenesis of Cri-du-chat syndrome.