PUBLICATION
The Central Nervous System Regulates Embryonic HSPC Production via Stress-Responsive Glucocorticoid Receptor Signaling
- Authors
- Kwan, W., Cortes, M., Frost, I., Esain, V., Theodore, L.N., Liu, S.Y., Budrow, N., Goessling, W., North, T.E.
- ID
- ZDB-PUB-170720-18
- Date
- 2016
- Source
- Cell Stem Cell 19: 370-82 (Journal)
- Registered Authors
- Goessling, Wolfram, North, Trista
- Keywords
- none
- MeSH Terms
-
- Serotonin/pharmacology
- Tryptophan Hydroxylase/metabolism
- Signal Transduction*/drug effects
- Cell Hypoxia/drug effects
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/metabolism
- Animals
- Cell Proliferation/drug effects
- Embryonic Stem Cells/drug effects
- Embryonic Stem Cells/metabolism*
- Serotonergic Neurons/drug effects
- Serotonergic Neurons/metabolism
- Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
- Fluoxetine/pharmacology
- Central Nervous System/metabolism*
- Sympathetic Nervous System/drug effects
- Sympathetic Nervous System/metabolism
- Kidney/drug effects
- Kidney/metabolism
- Receptors, Glucocorticoid/metabolism*
- Cell Count
- Hematopoietic Stem Cells/drug effects
- Hematopoietic Stem Cells/metabolism*
- Stress, Physiological/drug effects
- Zebrafish/embryology
- Hypothalamo-Hypophyseal System/drug effects
- Hypothalamo-Hypophyseal System/metabolism
- 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping