Modeling Movement Disorders via Generation of hiPSC-Derived Motor Neurons

Abstract

Generation of motor neurons (MNs) from human-induced pluripotent stem cells (hiPSCs) overcomes the limited access to human brain tissues and provides an unprecedent approach for modeling MN-related diseases. In this review, we discuss the recent progression in understanding the regulatory mechanisms of MN differentiation and their applications in the generation of MNs from hiPSCs, with a particular focus on two approaches: induction by small molecules and induction by lentiviral delivery of transcription factors. At each induction stage, different culture media and supplements, typical growth conditions and cellular morphology, and specific markers for validation of cell identity and quality control are specifically discussed. Both approaches can generate functional MNs. Currently, the major challenges in modeling neurological diseases using iPSC-derived neurons are: obtaining neurons with high purity and yield; long-term neuron culture to reach full maturation; and how to culture neurons more physiologically to maximize relevance to in vivo conditions.

Keywords: hiPSC; motor neurons; movement disorders; small molecules; transcription factors.

Figure 1

Generation of iPSC-derived MNs. (A) Schematic shows the process of generating iPSC-MNs. The culture media with different supplements are shown at different induction stages. (B) The timeline of the induction process from hiPSC to MNs. At each stage, specific markers and typical cellular morphology are shown. Image of MNs was adapted from [32].