A Modular Gain-of-Function Approach to Generate Cortical Interneuron Subtypes from ES Cells

作者：Au, Edmund; Ahmed, Tanzeel; Karayannis, Theofanis; Biswas, Shiona; Gan, Lin; Fishell, Gord^*

来源：Neuron, 2013, 80(5): 1145-1158.

DOI：10.1016/j.neuron.2013.09.022

• NEURAL STEM-CELLS
• CAUDAL GANGLIONIC EMINENCE
• FATE MAPPING REVEALS
• TRANSCRIPTION FACTORS
• DIRECTED DIFFERENTIATION
• BASAL FOREBRAIN
• NULL MUTATION
• DLX GENES
• MOUSE
• EXPRESSION

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 DIx2. 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.

• 出版日期2013-12-4
• 单位杭州师范大学