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.
Departamento de Fisiología Médica y Biofísica, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Seville, Spain.
Aida
A
Platero-Luengo
Instituto Cavanilles de Biodiversidad y Biología Evolutiva, Universidad de Valencia, 46071 Valencia, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 28031 Madrid, Spain.
Susana
S
González-Granero
Departamento de Fisiología Médica y Biofísica, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Seville, Spain.
Rocío
R
Durán
Departamento de Fisiología Médica y Biofísica, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Seville, Spain.
Blanca
B
Díaz-Castro
Departamento de Fisiología Médica y Biofísica, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Seville, Spain.
José I
JI
Piruat
Instituto Cavanilles de Biodiversidad y Biología Evolutiva, Universidad de Valencia, 46071 Valencia, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 28031 Madrid, Spain.
José Manuel
JM
García-Verdugo
Departamento de Fisiología Médica y Biofísica, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Seville, Spain. Electronic address: rpardal@us.es.
Ricardo
R
Pardal
Departamento de Fisiología Médica y Biofísica, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Seville, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 28031 Madrid, Spain. Electronic address: lbarneo@us.es.
José
J
López-Barneo
D000818:Animals; D002344:Carotid Body / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D051379:Mice; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D064828:Prolyl Hydroxylases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012125:Respiratory Center / Q000378:metabolism*
D064828:Prolyl Hydroxylases; D010100:Oxygen