As an indispensable component for the functions of the neurons system and signal initiator in all reflex responses, sensory neurons are major responsible for conveying internal, external, and environmental stimuli to the central nervous system (CNS). Damage to sensory neurons can lead to many diseases, such as traumatic injury, toxin exposure, immune system disorders, and metabolic disease. The subsequent cellular dysfunction leads to a loss of coordination involuntary movement. The in vitro source of human sensory neurons present great potentials in the generation of functional human disease models for drug discovery and pathological studies.
During the developmental stages of sensory neurons, a series of crucial signaling pathways are revealed. For example, the combination of Wnt signaling pathways and the TGF β super-family is important for sensory neuron differentiation. The neurotrophic factors for sensory neurons differentiation may include nerve growth factor (NGF), neurotrophin 3 (NT3), brain-derived neurotrophic factor (BDNF), and glial cell line-derived neurotrophic factor (GDNF).
Fig.1 Diferentiation of hESC to neural crest and sensory neural progenitors. (Alshawaf, 2018)
It has been proved that the functional sensory neurons can be generated from a human neural progenitor cell line hNP1, which is derived from the human embryonic stem cell line WA09. According to the cell treatment with trophic factors and chemicals that have shown important roles in sensory neurons generation, the hNP1 cell line is induced to generate sensory neurons. The immunocytochemical analysis is then used to confirm the identity of the sensory neurons. And the functional maturation of the differentiated sensory neurons can be determined by electrophysiological analysis. Compared with ESCs, the neural progenitor-based sensory neurons induction is simple, efficient, and faster. In addition, skin-derived precursor cells (SKP), as a type of neural crest stem cells, are also an important source of sensory neurons.
In conclusion, the generation of functional sensory neurons provides valuable tools for the simulation of in vitro functions of sensory neuron-related neural circuits and the treatment of related diseases.
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Reference
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