A modular gain-of-function approach to generate cortical interneuron subtypes from ES cells

Edmund Au, Tanzeel Ahmed, Theofanis Karayannis, Shiona Biswas, Lin Gan, Gord Fishell

Research output: Contribution to journalArticle

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 invitro.

Original languageEnglish (US)
Pages (from-to)1145-1158
Number of pages14
JournalNeuron
Volume80
Issue number5
DOIs
StatePublished - Dec 4 2013

ASJC Scopus subject areas

  • Neuroscience(all)

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