An O2-Sensitive Glomus Cell-Stem Cell Synapse Induces Carotid Body Growth in Chronic Hypoxia

Neural stem cells (NSCs) exist in germinal centers of the adult brain and in the carotid body (CB), an oxygen-sensing organ that grows under chronic hypoxemia. How stem cell lineage differentiation into mature glomus cells is coupled with changes in physiological demand is poorly understood. Here, we show that hypoxia does not affect CB NSC proliferation directly. Rather, mature glomus cells expressing endothelin-1, the O2-sensing elements in the CB that secrete neurotransmitters in response to hypoxia, establish abundant synaptic-like contacts with stem cells, which express endothelin receptors, and instruct their growth. Inhibition of glomus cell transmitter release or their selective destruction markedly diminishes CB cell growth during hypoxia, showing that CB NSCs are under the direct “synaptic” control of the mature O2-sensitive cells. Thus, glomus cells not only acutely activate the respiratory center but also induce NSC-dependent CB hypertrophy necessary for acclimatization to chronic hypoxemia. [Display omitted] •Acclimatization to hypoxia requires activation of stem cells and carotid body growth•Stem cells establish chemical synapses with neuron-like O2-sensitive glomus cells•Low pO2-induced transmitter release by glomus cells activates stem cell proliferation•Endothelin-1 and its receptors mediate glomus cell-stem cell communication Oxygen-sensing glomus cells establish synapses with neural stem cells in the carotid body, instructing their growth during hypoxia.