Imaging-based chemical screening reveals activity-dependent neural differentiation of pluripotent stem cells.

Journal: 
Elife
Publication Year: 
2013
Authors: 
Yaping Sun
Zhiqiang Dong
Taihao Jin
Kean-Hooi Ang
Miller Huang
Kelly M Haston
Jisong Peng
Tao P Zhong
Steven Finkbeiner
William A Weiss
Michelle R Arkin
Lily Y Jan
Su Guo
PubMed link: 
24040509
Public Summary: 
The role of mammalian pluripotent stem cells in neurodevelopment and neurodegenerative disorders
Scientific Abstract: 
Mammalian pluripotent stem cells (PSCs) represent an important venue for understanding basic principles regulating tissue-specific differentiation and discovering new tools that may facilitate clinical applications. Mechanisms that direct neural differentiation of PSCs involve growth factor signaling and transcription regulation. However, it is unknown whether and how electrical activity influences this process. Here we report a high throughput imaging-based screen, which uncovers that selamectin, an anti-helminthic therapeutic compound with reported activity on invertebrate glutamate-gated chloride channels, promotes neural differentiation of PSCs. We show that selamectin's pro-neurogenic activity is mediated by gamma2-containing GABAA receptors in subsets of neural rosette progenitors, accompanied by increased proneural and lineage-specific transcription factor expression and cell cycle exit. In vivo, selamectin promotes neurogenesis in developing zebrafish. Our results establish a chemical screening platform that reveals activity-dependent neural differentiation from PSCs. Compounds identified in this and future screening might prove therapeutically beneficial for treating neurodevelopmental or neurodegenerative disorders. DOI:http://dx.doi.org/10.7554/eLife.00508.001.