Cholinergic Signals from the CNS Regulate G-CSF-Mediated HSC Mobilization from Bone Marrow via a Glucocorticoid Signaling Relay.

ABSTRACT: Hematopoietic stem cells (HSCs) are mobilized from niches in the bone marrow (BM) to the blood circulation by the cytokine granulocyte colony-stimulating factor (G-CSF) through complex mechanisms. Among these, signals from the sympathetic nervous system regulate HSC egress via its niche, but how the brain communicates with the BM remains largely unknown. Here we show that muscarinic receptor type-1 (Chrm1) signaling in the hypothalamus promotes G-CSF-elicited HSC mobilization via hormonal priming of the hypothalamic-pituitary-adrenal (HPA) axis. Blockade of Chrm1 in the CNS, but not the periphery, reduces HSC mobilization. Mobilization is impaired in Chrm1^-∕- mice and rescued by parabiosis with wild-type mice, suggesting a relay by a blood-borne factor. We have identified the gl

SUBMITTER: Pierce H 

PROVIDER: S-EPMC5467872 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature