Single-Cell mRNA Profiling Reveals Cell-Type-Specific Expression of Neurexin Isoforms.
Single-Cell mRNA Profiling Reveals Cell-Type-Specific Expression of Neurexin Isoforms.
复制标题
DOI：
10.1016/j.neuron.2015.06.028
复制
发表时间：
2015-07-15
期刊：
影响因子：
16.2
通讯作者：
Südhof TC
中科院分区：
文献类型：
--
作者：
Fuccillo MV;Földy C;Gökce Ö;Rothwell PE;Sun GL;Malenka RC;Südhof TC
神经素被认为是与神经精神疾病有关的突触结构的中心组织者。神经素在数百种不同剪接亚型中的表达表明，单个神经元可能表现出细胞类型特异性的神经素表达模式（神经素代码）。为了验证这一假设，我们通过基于微流体的RT-PCR量化了神经素亚型和其他跨突触细胞粘附分子的单细胞水平。我们发现，神经蛋白库显示出明显的细胞类型特异性，这在每种类型的神经元中都是非常一致的。此外，我们还发现了神经蛋白转录和剪接位点使用的区域特异性调控。最后，我们证明了神经毒素的转录谱可以通过暴露于滥用药物以经验依赖的方式改变。我们的数据在单细胞水平上为多种神经素的细胞类型特异性表达模式提供了证据，并表明突触细胞粘附分子的表达与细胞身份和多样性的其他关键特征重叠。
Neurexins are considered central organizers of synapse architecture that are implicated in neuropsychiatric disorders. Expression of neurexins in hundreds of alternatively spliced isoforms suggested that individual neurons might exhibit a cell type-specific neurexin expression pattern (a neurexin code). To test this hypothesis, we quantified the single-cell levels of neurexin isoforms and other trans-synaptic cell-adhesion molecules by microfluidics-based RT-PCR. We show that the neurexin repertoire displays pronounced cell-type specificity that is remarkably consistent within each type of neuron. Furthermore, we uncovered region-specific regulation of neurexin transcription and splice-site usage. Finally, we demonstrate that the transcriptional profiles of neurexins can be altered in an experience-dependent fashion by exposure to a drug of abuse. Our data provide evidence of cell type-specific expression patterns of multiple neurexins at the single-cell level, and suggest that expression of synaptic cell-adhesion molecules overlaps with other key features of cellular identity and diversity.