An O2-sensitive glomus cell-stem cell synapse induces carotid body growth in chronic hypoxia

Aida Platero-Luengo, Susana González-Granero, Rocío Durán, Blanca Díaz-Castro, José I Piruat, José Manuel García-Verdugo, Ricardo Pardal, José López-Barneo

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)291-303
Number of pages13
JournalCell
Volume156
Issue number1-2
DOIs
Publication statusPublished - 16 Jan 2014

Keywords

  • Animals
  • Carotid Body/metabolism
  • Cell Differentiation
  • Cell Proliferation
  • Mice
  • Mice, Transgenic
  • Neural Stem Cells/metabolism
  • Oxygen/metabolism
  • Prolyl Hydroxylases/metabolism
  • Rats
  • Rats, Wistar
  • Respiratory Center/metabolism

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