Journal article
Directed differentiation and functional maturation of cortical interneurons from human embryonic stem cells
AM Maroof, S Keros, JA Tyson, SW Ying, YM Ganat, FT Merkle, B Liu, A Goulburn, EG Stanley, AG Elefanty, HR Widmer, K Eggan, PA Goldstein, SA Anderson, L Studer
Cell Stem Cell | CELL PRESS | Published : 2013
Abstract
Human pluripotent stem cells are a powerful tool for modeling brain development and disease. The human cortex is composed of two major neuronal populations: projection neurons and local interneurons. Cortical interneurons comprise a diverse class of cell types expressing the neurotransmitter GABA. Dysfunction of cortical interneurons has been implicated in neuropsychiatric diseases, including schizophrenia, autism, and epilepsy. Here, we demonstrate the highly efficient derivation of human cortical interneurons in an NKX2.1::GFP human embryonic stem cell reporter line. Manipulating the timing of SHH activation yields three distinct GFP+ populations with specific transcriptional profiles, neu..
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Awarded by Eunice Kennedy Shriver National Institute of Child Health and Human Development
Funding Acknowledgements
We would like to thank J. Hendrikx (Sloan-Kettering Institute [SKI] Flow Cytometry Core), A. Viale (SKI Genomics Core laboratory), M. Leversha (Molecular Cytogenetics Core), and E. Tu and M. Tomishima (SKI Stem Cell Facility) for excellent technical support. We further thank the Department of Gynecology (directors: M. Mueller and D. Surbek), University of Bern, Switzerland for providing us with the human fetal tissue. Studies using the NKX2.1::GFP hESC line were supported by grants from NYSTEM (S.A.), the European Commission project NeuroStemcell (L.S.), and the C.V. Starr Foundation (S.A. and L.S.). Experiments using hESC line WA-09 or iPSC lines were supported by NIMH grants 2RO1 MH066912 (S.A.) and 1RC1MH089690 (S.A. and L.S.) and by the Swiss National Science Foundation grant no. 31003A_135565 (H.R.W.).