Prospective isolation of cortical interneuron precursors from mouse embryonic stem cells.
Despite their therapeutic potential, progress in generating fully differentiated forebrain neurons from embryonic stem cells (ESCs) has lagged behind that from more caudal regions of the neuraxis. GABAergic interneuron precursors have the remarkable ability to migrate extensively and survive after transplantation into postnatal cortex, making them an attractive candidate for use in cell-based therapy for seizures or other neuropsychiatric disorders. We have modified a mouse ESC line with an Lhx6-GFP reporter construct that allows for the isolation of newly generated cortical interneuron precursors. When transplanted into postnatal cortex, these cells can migrate into the cortical parenchyma, survive for months, and display morphological, neurochemical, and electrophysiological properties characteristic of mature interneurons. This work demonstrates that forebrain neuronal subtypes with complex traits can be generated from embryonic stem cells, and provides a novel approach to the study of cortical interneuron development and to the establishment of cell-based therapies for neurological disease.
Maroof
Asif Mirza
AM
Program in Neuroscience, Weill Cornell Graduate School of Medical Sciences, Sloan Kettering Institute, and Department of Psychiatry, Weill Cornell Medical College, New York, New York 10065, USA.
Brown
Keith
K
Shi
Song-Hai
SH
Studer
Lorenz
L
Anderson
Stewart A
SA
D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D002469:Cell Separation; D002470:Cell Survival; D002540:Cerebral Cortex / Q000166:cytology*; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000637:transplantation; D017930:Genes, Reporter; D007150:Immunohistochemistry; D007395:Interneurons / Q000166:cytology* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D018408:Patch-Clamp Techniques; D013003:Somatosensory Cortex / Q000166:cytology