Transcriptomic and anatomic parcellation of 5-HT(3A)R expressing cortical interneuron subtypes revealed by single-cell RNA sequencing.
Transcriptomic and anatomic parcellation of 5-HT(3A)R expressing cortical interneuron subtypes revealed by single-cell RNA sequencing.
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DOI：
10.1038/ncomms14219
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发表时间：
2017-01-30
影响因子：
16.6
通讯作者：
Dayer A
中科院分区：
文献类型：
--
作者：
Frazer S;Prados J;Niquille M;Cadilhac C;Markopoulos F;Gomez L;Tomasello U;Telley L;Holtmaat A;Jabaudon D;Dayer A
皮层GABA能中间神经元构成了高度多样化的抑制性神经元群体，这些抑制性神经元是皮层微电路功能的关键调节器。一个重要的和异质性的皮质中间神经元组特异性表达5-羟色胺受体3A（5-HT 3AR），但这种多样性如何在发育过程中出现知之甚少。在这里，我们使用单细胞转录组学，以确定基因的表达模式在Htr 3a-GFP+中间神经元在皮层电路组装的早期步骤。我们确定了三种主要的分子类型的Htr 3a-GFP+中间神经元，每一个显示不同的基因表达的发育动力学。转录因子Meis 2特异性地富集在主要局限于皮质白色物质的Htr 3 a-GFP+中间神经元类型中。这些MEIS 2表达的中间神经元似乎起源于位于胚胎苍白球-苍白球下边界的限制区域。总体而言，这项研究确定MEIS 2作为一个亚类特异性标记5-HT 3AR含间质神经元，并表明，皮层中间神经元的转录和解剖parcellation发育耦合。皮质GABA能中间神经元在其基因表达、电生理特性和连接性方面高度多样。在这里，作者使用单细胞RNA-seq方法揭示了Htr 3a-GFP+中间神经元的三种不同亚型，并将MEIS 2鉴定为一种这样的亚型的标志物。
Cortical GABAergic interneurons constitute a highly diverse population of inhibitory neurons that are key regulators of cortical microcircuit function. An important and heterogeneous group of cortical interneurons specifically expresses the serotonin receptor 3A (5-HT3AR) but how this diversity emerges during development is poorly understood. Here we use single-cell transcriptomics to identify gene expression patterns operating in Htr3a-GFP+ interneurons during early steps of cortical circuit assembly. We identify three main molecular types of Htr3a-GFP+ interneurons, each displaying distinct developmental dynamics of gene expression. The transcription factor Meis2 is specifically enriched in a type of Htr3a-GFP+ interneurons largely confined to the cortical white matter. These MEIS2-expressing interneurons appear to originate from a restricted region located at the embryonic pallial–subpallial boundary. Overall, this study identifies MEIS2 as a subclass-specific marker for 5-HT3AR-containing interstitial interneurons and demonstrates that the transcriptional and anatomical parcellation of cortical interneurons is developmentally coupled. Cortical GABAergic interneurons are highly diverse in their gene expression, electrophysiological properties, and connectivity. Here the authors reveal three distinct subtypes of Htr3a-GFP+ interneurons using the single-cell RNA-seq approach, and identify MEIS2 as a marker for one such subtype.