Classifying Drosophila Olfactory Projection Neuron Subtypes by Single-Cell RNA Sequencing.
Hongjie Li, Felix Horns, Bing Wu, Qijing Xie, Jiefu Li, Tongchao Li, David J Luginbuhl, Stephen R Quake, Liqun Luo
Author Information
Hongjie Li: Department of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Felix Horns: Biophysics Graduate Program, Stanford University, Stanford, CA 94305, USA.
Bing Wu: Department of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Qijing Xie: Department of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA; Neurosciences Graduate Program, Stanford University, Stanford, CA 94305, USA.
Jiefu Li: Department of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Tongchao Li: Department of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
David J Luginbuhl: Department of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Stephen R Quake: Departments of Bioengineering and Applied Physics, Stanford University, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, Stanford, CA 94305, USA. Electronic address: quake@stanford.edu.
Liqun Luo: Department of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA. Electronic address: lluo@stanford.edu.
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.
