title: Molecular profiling of activated olfactory neurons identifies odorant receptors for odors in vivo.
abstract: The mammalian olfactory system uses a large family of odorant receptors (ORs) to detect and discriminate amongst a myriad of volatile odor molecules. Understanding odor coding requires comprehensive mapping between ORs and corresponding odors. We developed a means of high-throughput in vivo identification of OR repertoires responding to odorants using phosphorylated ribosome immunoprecipitation of mRNA from olfactory epithelium of odor-stimulated mice followed by RNA-Seq. This approach screened the endogenously expressed ORs against an odor in one set of experiments using awake and freely behaving mice. In combination with validations in a heterologous system, we identified sets of ORs for two odorants, acetophenone and 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), encompassing 69 OR-odorant pairs. We also identified shared amino acid residues specific to the acetophenone or TMT receptors and developed models to predict receptor activation by acetophenone. Our results provide a method for understanding the combinatorial coding of odors in vivo.
authors: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA.|University Program in Genetics and Genomics, Duke University Medical Center, Durham, North Carolina, USA.|Department of Statistical Science, Duke University, Durham, North Carolina, USA.
authors: Yue
authors: Y
authors: Jiang
authors: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA.
authors: Naihua Natalie
authors: NN
authors: Gong
authors: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA.
authors: Xiaoyang Serene
authors: XS
authors: Hu
authors: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA.
authors: Mengjue Jessica
authors: MJ
authors: Ni
authors: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA.
authors: Radhika
authors: R
authors: Pasi
authors: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA.|Department of Neurobiology, Duke Institute for Brain Sciences, Duke University Medical Center, Durham, North Carolina, USA.
authors: Hiroaki
authors: H
authors: Matsunami
mesh_terms: D000818:Animals; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism*; D018034:Olfactory Receptor Neurons / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D018035:Receptors, Odorant / Q000378:metabolism*; D012903:Smell / Q000502:physiology
chemical_list: D018035:Receptors, Odorant