Journal
CELL REPORTS
Volume 16, Issue 7, Pages 1942-1953Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2016.07.035
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Funding
- Singapore Ministry of Education (MOE) Academic Research Fund [MOE2012-T2-1-021, MOE2014-T2-071]
- A*Star Translational Collaborative Research Partnership Grant (TCRP) [13/1/96/688]
- Singapore National Medical Research Council Research Grant [NMRC/CBRG/0075/2014]
- Duke-NUS Signature Research Program Block Grant
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Gamma-aminobutyric acid (GABA)-releasing interneurons play an important modulatory role in the cortex and have been implicated inmultiple neurological disorders. Patient-derived interneurons could provide a foundation for studying the pathogenesis of these diseases as well as for identifying potential therapeutic targets. Here, we identified a set of genetic factors that could robustly induce human pluripotent stem cells (hPSCs) into GABAergic neurons (iGNs) with high efficiency. We demonstrated that the human iGNs express neurochemical markers and exhibit mature electrophysiological properties within 6-8 weeks. Furthermore, in vitro, iGNs could form functional synapses with other iGNs or with human-induced glutamatergic neurons (iENs). Upon transplantation into immunodeficient mice, human iGNs underwent synaptic maturation and integration into host neural circuits. Taken together, our rapid and highly efficient single-step protocol to generate iGNs may be useful to both mechanistic and translational studies of human interneurons.
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