Oxygen regulation of breathing through an olfactory receptor activated by lactate

Animals have evolved homeostatic responses to changes in oxygen availability that act on different timescales. Although the hypoxia-inducible factor (HIF) transcriptional pathway that controls long-term responses to low oxygen (hypoxia) has been established, the pathway that mediates acute responses to hypoxia in mammals is not well understood. Here we show that the olfactory receptor gene Olfr78 is highly and selectively expressed in oxygen-sensitive glomus cells of the carotid body, a chemosensory organ at the carotid artery bifurcation that monitors blood oxygen and stimulates breathing within seconds when oxygen declines. Olfr78 mutants fail to increase ventilation in hypoxia but respond normally to hypercapnia. Glomus cells are present in normal numbers and appear structurally intact, but hypoxia-induced carotid body activity is diminished. Lactate, a metabolite that rapidly accumulates in hypoxia and induces hyperventilation, activates Olfr78 in heterologous expression experiments, induces calcium transients in glomus cells, and stimulates carotid sinus nerve activity through Olfr78. We propose that, in addition to its role in olfaction, Olfr78 acts as a hypoxia sensor in the breathing circuit by sensing lactate produced when oxygen levels decline

Progenitor cell heterogeneity in the adult carotid body germinal niche

Somatic stem cells confer plasticity to adult tissues, permitting their maintenance, repair and adaptation to a changing environment. Adult germinal niches supporting somatic stem cells have been thoroughly characterized throughout the organism, including in central and peripheral nervous systems. Stem cells do not reside alone within their niches, but they are rather accompanied by multiple progenitor cells that not only contribute to the progression of stem cell lineage but also regulate their behavior. Understanding the mechanisms underlying these interactions within the niche is crucial to comprehend associated pathologies and to use stem cells in cell therapy. We have described a stunning germinal niche in the adult peripheral nervous system: the carotid body. This is a chemoreceptor organ with a crucial function during physiological adaptation to hypoxia. We have shown the presence of multipotent stem cells within this niche, escorted by multiple restricted progenitor cell types that contribute to niche physiology and hence organismal adaptation to the lack of oxygen. Herein, we discuss new and existing data about the nature of all these stem and progenitor cell types present in the carotid body germinal niche, discussing their role in physiology and their clinical relevance for the treatment of diverse pathologies.Peer reviewe