Directing neuronal cell fatein vitro: Achievements and challenges

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Human pluripotent stem cell (PSC) technology and direct somatic cell reprogramming have opened up a promising new avenue in the field of neuroscience. These recent advances allow researchers to obtain virtually any cell type found in the human brain, making it possible to produce and study functional neurons in laboratory conditions for both scientific and medical purposes. Although distinct approaches have shown to be successful in directing neuronal cell fate in vitro, their refinement and optimization, as well as the search for alternative approaches, remains necessary to help realize the full potential of the eventually derived neuronal populations. Furthermore, we are currently limited in the number of neuronal subtypes whose induction is fully established, and different cultivation protocols for each subtype exist, making it challenging to increase the reproducibility and decrease the variances that are observed between different protocols. In this review, we summarize the progress that has been made in generating various neuronal subtypes from PSCs and somatic cells, with special emphasis on chemically defined systems, transcription factor-mediated reprogramming and epigenetic-based approaches. We also discuss the efforts that are being made to increase the efficiency of current protocols and address the potential for the use of these cells in disease modelling, drug discovery and regenerative medicine.HighlightsDirected differentiation and reprogramming of stem cells and somatic cells allow induction of human neurons in vitro.Chemical stimulation for in vitro differentiation recapitulates the neurodevelopmental patterning principles in the embryo.Overexpression of transcription factors induces dramatic changes in transcriptional networks that drive cellular conversions.Epigenetic manipulation allows induction of profound epigenome remodelling processes that underlie cell fate switches.The availability of human neurons in vitro has critical implications for future brain-related studies and drug development.

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