Li Hongjie, Horns Felix, Wu Bing, Xie Qijing, Li Jiefu, Li Tongchao, Luginbuhl David J, Quake Stephen R, Luo Liqun
Department of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Biophysics Graduate Program, Stanford University, Stanford, CA 94305, USA.
Cell. 2017 Nov 16;171(5):1206-1220.e22. doi: 10.1016/j.cell.2017.10.019.
The definition of neuronal type and how it relates to the transcriptome are open questions. Drosophila olfactory projection neurons (PNs) are among the best-characterized neuronal types: different PN classes target dendrites to distinct olfactory glomeruli, while PNs of the same class exhibit indistinguishable anatomical and physiological properties. Using single-cell RNA sequencing, we comprehensively characterized the transcriptomes of most PN classes and unequivocally mapped transcriptomes to specific olfactory function for six classes. Transcriptomes of closely related PN classes exhibit the largest differences during circuit assembly but become indistinguishable in adults, suggesting that neuronal subtype diversity peaks during development. Transcription factors and cell-surface molecules are the most differentially expressed genes between classes and are highly informative in encoding cell identity, enabling us to identify a new lineage-specific transcription factor that instructs PN dendrite targeting. These findings establish that neuronal transcriptomic identity corresponds with anatomical and physiological identity defined by connectivity and function.
神经元类型的定义及其与转录组的关系仍是悬而未决的问题。果蝇嗅觉投射神经元（PNs）是特征最为明确的神经元类型之一：不同类别的PN将树突靶向不同的嗅觉小球，而同一类别的PN表现出难以区分的解剖学和生理学特性。利用单细胞RNA测序，我们全面表征了大多数PN类别的转录组，并明确地将六个类别的转录组映射到特定的嗅觉功能。密切相关的PN类别的转录组在神经回路组装过程中表现出最大差异，但在成体中变得难以区分，这表明神经元亚型多样性在发育过程中达到峰值。转录因子和细胞表面分子是不同类别之间差异表达最大的基因，在编码细胞身份方面具有高度信息性，使我们能够鉴定出一种指导PN树突靶向的新的谱系特异性转录因子。这些发现表明，神经元转录组身份与由连接性和功能定义的解剖学和生理学身份相对应。
