Induced Pluripotent Stem Cells (iPSCs) are pluripotent stem cells that can be generated
from somatic cells, and provide a way to model the development of neural tissues in
vitro. One particularly interesting application of iPSCs is the development of neurons
analogous to those found in the human forebrain. Forebrain neurons play a central
role in cognition and sensory processing, and deficits in forebrain neuronal activity
contributes to a host of conditions, including epilepsy, Alzheimer's disease, and
schizophrenia. Here, we present our protocol for differentiating iPSCs into forebrain
neural progenitor cells (NPCs) and neurons, whereby neural rosettes are generated
from stem cells without dissociation and NPCs purified from rosettes based on their
adhesion, resulting in a more rapid generation of pure NPC cultures. Neural progenitor
cells can be maintained as long-term cultures, or differentiated into forebrain neurons.
This protocol provides a simplified and fast methodology of generating forebrain NPCs
and neurons, and enables researchers to generate effective in vitro models to study
forebrain disease and neurodevelopment. This protocol can also be easily adapted to
generate other neural lineages.