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Cell. 2017 Nov 16;171(5):1206-1220.e22. doi: 10.1016/j.cell.2017.10.019.

Classifying Drosophila Olfactory Projection Neuron Subtypes by Single-Cell RNA Sequencing.

Author information

1
Department of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
2
Biophysics Graduate Program, Stanford University, Stanford, CA 94305, USA.
3
Department of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA; Neurosciences Graduate Program, Stanford University, Stanford, CA 94305, USA.
4
Departments of Bioengineering and Applied Physics, Stanford University, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, Stanford, CA 94305, USA. Electronic address: quake@stanford.edu.
5
Department of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA. Electronic address: lluo@stanford.edu.

Abstract

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.

KEYWORDS:

Drosophila; Single-cell RNA-seq; cell type; combinatorial code; connectivity; development; neuronal identity; olfactory system; projection neuron; transcriptome

PMID:
29149607
PMCID:
PMC6095479
DOI:
10.1016/j.cell.2017.10.019
[Indexed for MEDLINE]
Free PMC Article

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