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<p>Adaptive homeostatic responses to oxygen (O<sub>2</sub>) deficiency (hypoxia) are essential for survival. The prototypical acute O<sub>2</sub>-sensing organ is the carotid body (CB), a neural crest-derived tissue with chemoreceptor glomus cells that express hypoxia-inhibited K<sup>+</sup> 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 O<sub>2</sub> 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 O<sub>2</sub>-sensing neuronal cell lineage (multipotent progenitors, neuroblasts, and mature glomus cells). Acclimatization to chronic hypoxia involves the rapid conversion of neuroblasts into mature O<sub>2</sub>-sensitive chemoreceptor cells and enhancement of the glomus cell O<sub>2</sub>-sensing and neurosecretory genetic profile.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月28日

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  • Ana Santamaría-Santiago,
  • Verónica Sobrino,
  • Luis Luna-Ramírez,
  • José López-Barneo,
  • Ricardo Pardal

摘要

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.