Genetic map of the carotid body stem cell niche with focus on the O2-sensing chemoreceptor cell lineage.

Adaptive homeostatic responses to oxygen (O₂) deficiency (hypoxia) are essential for survival. The prototypical acute O₂-sensing organ is the carotid body (CB), a neural crest-derived tissue with chemoreceptor glomus cells that express hypoxia-inhibited K⁺ channels. This, in turn, leads to neurotransmitter release and the activation of nerve fibers terminating in the brainstem, evoking hyperventilation. The adult CB contains a population of multipotent stem cells capable of proliferating and differentiating into new chemoreceptor cells, supporting its growth during acclimatization to chronic hypoxia. The responsiveness of glomus cells to hypoxia relies on the constitutive expression of HIF2α and a set of HIF2α-dependent genes, which define a mitochondria-to-membrane signaling pathway for acute O₂ sensing. The genetic profiles of the various cell types within the CB, and how they change in response to sustained hypoxia, remain unknown. Here, we present a complete transcriptomic map of the CB, with an emphasis on the characterization of genetic profiles of the acute O₂-sensing neuronal cell lineage (multipotent progenitors, neuroblasts, and mature glomus cells). Acclimatization to chronic hypoxia involves the rapid conversion of neuroblasts into mature O₂-sensitive chemoreceptor cells and enhancement of the glomus cell O₂-sensing and neurosecretory genetic profile.