Regulation of the hematopoietic bone marrow niche. The sympathetic nervous system (SNS) exerts control on the HSC niche by the circadian release of catecholamine, which targets β3-adrenergic receptors on stroma cells. The same signals can act through neutrophils to produce prostaglandin E2 (PGE₂) and stimulate the osteoblastic niche. The stromal niche is also circadianally regulated by aged neutrophils that return to the bone marrow after only several hours in the circulation. Aged neutrophils that infiltrate the bone marrow are engulfed by macrophages and activation of the LXRs lead to inhibition of the hematopoietic niche. Excessive G-CSF production associated with several inflammatory processes or impaired neutrophil clearance in extramedullary tissues is also a potent inhibitor of the HSPC niche. All of these regulatory mechanisms ultimately inhibit production of CXCL12, thereby promoting HSPC egress into blood. This has been shown in the intestine, where neutrophil infiltration in the mucosa and engulfment of neutrophils by tissue-resident macrophages inhibits the IL-23/IL-17/G-CSF axis and remotely supports niche activity in a circadian-independent manner. Boxes indicate the presence or absence of circadian oscillations in each tissue. Professional illustration by Patrick Lane, ScEYEnce Studios.