title: A modular gain-of-function approach to generate cortical interneuron subtypes from ES cells.
abstract: Whereas past work indicates that cortical interneurons (cINs) can be generically produced from stem cells, generating large numbers of specific subtypes of this population has remained elusive. This reflects an information gap in our understanding of the transcriptional programs required for different interneuron subtypes. Here, we have utilized the directed differentiation of stem cells into specific subpopulations of cortical interneurons as a means to identify some of these missing factors. To establish this approach, we utilized two factors known to be required for the generation of cINs, Nkx2-1 and Dlx2. As predicted, their regulated transient expression greatly improved the differentiation efficiency and specificity over baseline. We extended upon this "cIN-primed" model in order to establish a modular system whereby a third transcription factor could be systematically introduced. Using this approach, we identified Lmo3 and Pou3f4 as genes that can augment the differentiation and/or subtype specificity of cINs in vitro.
authors: NYU Neuroscience Institute, NYU Langone Medical Center, 522 First Avenue, New York, NY 10016, USA; New York University School of Medicine, NYU Langone Medical Center, 522 First Avenue, New York, NY 10016, USA.
authors: Edmund
authors: E
authors: Au
authors: Tanzeel
authors: T
authors: Ahmed
authors: Theofanis
authors: T
authors: Karayannis
authors: Shiona
authors: S
authors: Biswas
authors: Lin
authors: L
authors: Gan
authors: Gord
authors: G
authors: Fishell
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D019070:Cell Lineage; D002540:Cerebral Cortex / Q000166:cytology*; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D007395:Interneurons / Q000145:classification* / Q000502:physiology*; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D018408:Patch-Clamp Techniques; D033581:Stem Cell Transplantation; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; D009419:Nerve Tissue Proteins; C000614414:Nkx2-1 protein, mouse; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D049452:Green Fluorescent Proteins