A Common Mechanism of Singular Gene Choice is Revealed by Broadly Expressed Odorant Receptor ​​Transgenes within the Olfactory Epithelium

In the mouse, more than 1,100 odorant receptors (ORs) are expressed in a monogenic and monoallelic fashion, referred to as singular gene expression. Here we utilize multimers of a naturally occurring 21bp enhancer (x21) and radically increase the number of olfactory sensory neurons (OSNs) choosing an OR transgene that is normally expressed by Class II cell types. Surprisingly, hundreds of ORs derived from Class I, Class II and TAAR cell types have reduced expression and are replaced by the OR transgene expression leading to novel glomeruli formed in three segregating domains of glomeruli on the olfactory bulb: DI (Class I), DII (Class II), and DIII (TAAR). The reduction of expression across distinct cell types that were thought to have distinct mechanisms of singular gene choice in favor of the expression of the x21-OR transgene argues that a common mechanism of singular gene choice is present for all OR-expressing OSNs. We have employed a single cell RNA sequencing approach using 10x Genomics scRNAseq to study odorant receptor gene expression profile in our transgenic mouse and wildtype mouse of olfactory sensory neurons and the precursor cells.