Characterizing Human Stem Cell–derived Sensory Neurons at the Single-cell Level Reveals Their Ion Channel Expression and Utility in Pain Research

• Published in: Molecular therapy Vol. 22; no. 8; pp. 1530 - 1543
• Main Authors: Young, Gareth T, Gutteridge, Alex, Fox, Heather DE, Wilbrey, Anna L, Cao, Lishuang, Cho, Lily T, Brown, Adam R, Benn, Caroline L, Kammonen, Laura R, Friedman, Julia H, Bictash, Magda, Whiting, Paul, Bilsland, James G, Stevens, Edward B
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2014; Elsevier Limited; Nature Publishing Group
• Subjects: Acids; Aniline Compounds - pharmacology; Brain-derived neurotrophic factor; Cell Differentiation; Cells, Cultured; Colforsin - pharmacology; Disease; Furans - pharmacology; Ganglia, Spinal - physiology; Gene expression; Gene Expression Regulation; Humans; Ion Channels - genetics; Neurons; Original; Pain; Pain - physiopathology; Physiology; Pluripotent Stem Cells - metabolism; R&D; Regenerative medicine; Research & development; Sensory Receptor Cells - cytology; Sensory Receptor Cells - physiology; Single-Cell Analysis; Stem cells; Vascular endothelial growth factor; United Kingdom > UK
• ISSN: 1525-0016; 1525-0024
• DOI: 10.1038/mt.2014.86

The generation of human sensory neurons by directed differentiation of pluripotent stem cells opens new opportunities for investigating the biology of pain. The inability to generate this cell type has meant that up until now their study has been reliant on the use of rodent models. Here, we use a combination of population and single-cell techniques to perform a detailed molecular, electrophysiological, and pharmacological phenotyping of sensory neurons derived from human embryonic stem cells. We describe the evolution of cell populations over 6 weeks of directed differentiation; a process that results in the generation of a largely homogeneous population of neurons that are both molecularly and functionally comparable to human sensory neurons derived from mature dorsal root ganglia. This work opens the prospect of using pluripotent stem-cell–derived sensory neurons to study human neuronal physiology and as in vitro models for drug discovery in pain and sensory disorders.