Molecular characterization of projection neuron subtypes in the mouse olfactory bulb.
Molecular characterization of projection neuron subtypes in the mouse olfactory bulb.
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DOI：
10.7554/elife.65445
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发表时间：
2021-07-22
期刊：
影响因子：
7.7
通讯作者：
Fleischmann A
中科院分区：
文献类型：
--
作者：
Zeppilli S;Ackels T;Attey R;Klimpert N;Ritola KD;Boeing S;Crombach A;Schaefer AT;Fleischmann A
哺乳动物嗅球中的投射神经元接受来自鼻子的信息并投射到不同的皮层和皮层下区域。形态学和生理学研究强调了功能异质性，但没有描述描述PN亚型的分子标记物。在这里，我们使用病毒注射到嗅觉皮层和荧光核分选来富集PN，用于高通量单核和批量RNA深度测序。转录组分析和RNA原位杂交确定了不同的二尖瓣和簇状细胞群体的特征性转录因子网络拓扑结构，细胞粘附和兴奋性相关的基因表达。最后，我们描述了一种新的计算方法，用于整合批量和snRNA-seq数据，并提供证据表明不同的二尖瓣细胞群优先投射到不同的靶区域。总之，我们已经确定了潜在的分子和基因调控机制的PN多样性，并提供新的分子切入点，研究二尖瓣和簇状细胞亚型的不同功能的作用。
Projection neurons (PNs) in the mammalian olfactory bulb (OB) receive input from the nose and project to diverse cortical and subcortical areas. Morphological and physiological studies have highlighted functional heterogeneity, yet no molecular markers have been described that delineate PN subtypes. Here, we used viral injections into olfactory cortex and fluorescent nucleus sorting to enrich PNs for high-throughput single nucleus and bulk RNA deep sequencing. Transcriptome analysis and RNA in situ hybridization identified distinct mitral and tufted cell populations with characteristic transcription factor network topology, cell adhesion, and excitability-related gene expression. Finally, we describe a new computational approach for integrating bulk and snRNA-seq data and provide evidence that different mitral cell populations preferentially project to different target regions. Together, we have identified potential molecular and gene regulatory mechanisms underlying PN diversity and provide new molecular entry points into studying the diverse functional roles of mitral and tufted cell subtypes.