Pluripotent stem cell‐derived neurons represent a potentially limitless supply of human neurons to model diseases, replace diseased or dysfunctional tissue and to identify novel therapeutics to treat disease. Despite the incredible potential that human stem cell‐derived neurons represent, genetic, cellular and developmental obstacles represent substantial roadblocks to realizing this potential. Current schemes used to generate neurons from pluripotent stem cells rely on incomplete knowledge of human brain development, and often generate heterogeneous and immature neuronal populations. Recent technological advances in synthetic biology, genome engineering and single cell analysis have provided new tools for biologists to advance both our understanding and use of stem cell‐derived neurons. These advances should help overcome the pitfalls of pluripotent stem cells to generate homogeneous, mature neuronal subtypes relevant to disease and to realise the therapeutic promise of human stem cell‐derived neurons.
The ability to generate pluripotent stem cells from adult somatic cells now gives researchers unprecedented access to human neurons for disease modelling, cell replacement therapy and high throughput screening.
Our incomplete understanding of human brain development is an obstacle to deriving human neurons in vitro that mimic their in vivo counterparts.
Current differentiation schemes allow researchers to derive motor neurons, excitatory and inhibitory neurons of the human cortex and other neuronal subtypes.
Subtle differences in the derivation or differentiation of pluripotent stem cells can have profound functional consequences for neurons derived from them.
Genome editing techniques are poised to allow researchers to generate even more useful cellular tools by engineering mutations and reporters into pluripotent stem cells.
Keywords: pluripotent stem cell; neuronal differentiation; neural induction; disease models; genome editing; CRISPR; Cas9