Utilizing human induced pluripotent stem cells and derived models to study neurodevelopment and neurodegenerative disease

Abstract

Human induced pluripotent stem cells (hiPSCs) and derived models are increasingly being used to model gene-environmental interactions relevant to neurodegenerative diseases as well as reveal novel functions of apoptotic machinery in neurodevelopment. Vulnerability of hiPSC-derived neurons to toxicants, such as heavy metals and pesticides, can be assessed in patient specific cellular model and this chapter will outline approaches for using hiPSCs to model gene by environment interactions in neurotoxicity and neurodegenerative disease. We emphasize the adaptation of basic cellular-based outcome measures related to mitochondrial dysfunction, oxidative stress, and changes in neuronal morphology. Additionally, this chapter will have a specific focus on mitochondrial dynamics, which are speculated to model cell fate and control developmental apoptosis both of which are pertinent for neurodevelopment. Recent studies show that mitochondrial morphology and function play major roles in not only maintaining but also regulating identity of cells in neurodevelopment. Alterations in the processes mentioned in this study can lead to severe consequences for neurodevelopment and neurodegenerative disease.