Olfactory sensory neurons transiently express multiple olfactory receptors during development

In mammals, each olfactory sensory neuron randomly expresses one, and only one, olfactory receptor (OR)—a phenomenon called the “one‐neuron‐one‐receptor” rule. Although extensively studied, this rule was never proven for all ~1,000 OR genes in one cell at once, and little is known about its dynamics. Here, we directly tested this rule by single‐cell transcriptomic sequencing of 178 cells from the main olfactory epithelium of adult and newborn mice. To our surprise, a subset of cells expressed multiple ORs. Most of these cells were developmentally immature. Our results illustrated how the “one‐neuron‐one‐receptor” rule may have been established: At first, a single neuron temporarily expressed multiple ORs—seemingly violating the rule—and then all but one OR were eliminated. This work provided experimental evidence that epigenetic regulation in the olfactory system selects a single OR by suppressing a few transiently expressed ORs in a single cell during development.