ZFIN ID: ZDB-PUB-170720-18 |
The Central Nervous System Regulates Embryonic HSPC Production via Stress-Responsive Glucocorticoid Receptor Signaling
Kwan, W., Cortes, M., Frost, I., Esain, V., Theodore, L.N., Liu, S.Y., Budrow, N., Goessling, W., North, T.E.
Date: | 2016 |
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Source: | Cell Stem Cell 19: 370-82 (Journal) |
Registered Authors: | Goessling, Wolfram, North, Trista |
Keywords: | none |
MeSH Terms: |
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PubMed: | 27424782 Full text @ Cell Stem Cell |
Citation
Kwan, W., Cortes, M., Frost, I., Esain, V., Theodore, L.N., Liu, S.Y., Budrow, N., Goessling, W., North, T.E. (2016) The Central Nervous System Regulates Embryonic HSPC Production via Stress-Responsive Glucocorticoid Receptor Signaling. Cell Stem Cell. 19:370-82.
ABSTRACT
Hematopoietic stem and progenitor cell (HSPC) specification is regulated by numerous defined factors acting locally within the hemogenic niche; however, it is unclear whether production can adapt to fluctuating systemic needs. Here we show that the CNS controls embryonic HSPC numbers via the hypothalamic-pituitary-adrenal/interrenal (HPA/I) stress response axis. Exposure to serotonin or the reuptake inhibitor fluoxetine increased runx1 expression and Flk1(+)/cMyb(+) HSPCs independent of peripheral innervation. Inhibition of neuronal, but not peripheral, tryptophan hydroxlyase (Tph) persistently reduced HSPC number. Consistent with central HPA/I axis induction and glucocorticoid receptor (GR) activation, GR agonists enhanced, whereas GR loss diminished, HSPC formation. Significantly, developmental hypoxia, as indicated by Hif1α function, induced the HPA/I axis and cortisol production. Furthermore, Hif1α-stimulated HSPC enhancement was attenuated by neuronal tph or GR loss. Our data establish that embryonic HSC production responds to physiologic stress via CNS-derived serotonin synthesis and central feedback regulation to control HSC numbers.
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