Single-Cell Transcriptomes Reveal Diverse Regulatory Strategies for Olfactory Receptor Expression and Axon Targeting.
Hongjie Li, Tongchao Li, Felix Horns, Jiefu Li, Qijing Xie, Chuanyun Xu, Bing Wu, Justus M Kebschull, Colleen N McLaughlin, Sai Saroja Kolluru, Robert C Jones, David Vacek, Anthony Xie, 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. Electronic address: hongjie@stanford.edu.
Tongchao 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; Department of Bioengineering and Department of Applied Physics, Stanford University, Stanford, CA 94305, USA.
Jiefu Li: 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.
Chuanyun Xu: Department of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Bing Wu: Department of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Justus M Kebschull: Department of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Colleen N McLaughlin: Department of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Sai Saroja Kolluru: Department of Bioengineering and Department of Applied Physics, Stanford University, Stanford, CA 94305, USA.
Robert C Jones: Department of Bioengineering and Department of Applied Physics, Stanford University, Stanford, CA 94305, USA.
David Vacek: Department of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Anthony Xie: 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: Department of Bioengineering and Department of 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 regulatory mechanisms by which neurons coordinate their physiology and connectivity are not well understood. The Drosophila olfactory receptor neurons (ORNs) provide an excellent system to investigate this question. Each ORN type expresses a unique olfactory receptor, or a combination thereof, and sends their axons to a stereotyped glomerulus. Using single-cell RNA sequencing, we identified 33 transcriptomic clusters for ORNs and mapped 20 to their glomerular types, demonstrating that transcriptomic clusters correspond well with anatomically and physiologically defined ORN types. Each ORN type expresses hundreds of transcription factors. Transcriptome-instructed genetic analyses revealed that (1) one broadly expressed transcription factor (Acj6) only regulates olfactory receptor expression in one ORN type and only wiring specificity in another type, (2) one type-restricted transcription factor (Forkhead) only regulates receptor expression, and (3) another type-restricted transcription factor (Unplugged) regulates both events. Thus, ORNs utilize diverse strategies and complex regulatory networks to coordinate their physiology and connectivity.
