Generation of Glutamatergic Human Neurons from Induced Pluripotent Stem Cells

Generation of human induced pluripotent stem cells (iPSCs) provided a unique platform for human brain development studies, in vitro disease modeling, and therapeutic strategy development. Human stem cells can be rapidly and efficiently differentiated into several distinct subpopulations of brain cells. These stem cell-derived systems are gaining acceptance as a viable alternative in the neuroscience field as they can mimic interactions between various brain cells, and help recapitulate brain regions with specific functions. Here, we describe a method to generate functional, postmitotic, excitatory cortical-like neurons from iPSCs by expressing the NGN2 transgene from a stably integrated doxycycline-inducible promoter. These induced neurons (iNs) can be utilized to study the development and function of human cortical neurons. They also allow studying disease mechanisms by comparing normal and pathophysiological conditions and enable reliable screens for testing of therapeutic approaches.