Circadian rhythms, adrenergic hormones and trafficking of hematopoietic stem cells.
BACKGROUND
Under homeostasis, small numbers of haematopoietic stem cells (HSCs) are detectable in the bloodstream of mammals, but the mechanisms of their trafficking are unknown.


METHODS
It has been shown that circulating HSCs exhibit marked circadian fluctuations due to standard cycles of 12 h light/12 h darkness. Circadian HSCs oscillations are strongly altered when mice are subjected to continuous light for two weeks or to a jet lag. In addition, circulating HSCs fluctuate in antiphase with the expression of the chemokine CXCL12 in the bone marrow microenvironment. Circadian HSC trafficking and expression of CXCL12 are modulated by core genes of the central clock through rhythmic secretion of adrenergic hormones from nerve terminals of the sympathetic nervous system (SNS) in the bone marrow.


RESULTS
This review summarizes recent findings on the circadian regulation of HSC release in the bone marrow examining the molecular mechanisms through which the central molecular clock regulates CXCL12 in bone marrow stromal cells through rhythmic secretion of adrenergic hormones locally delivered in the bone marrow by nerve terminals from the SNS.


CONCLUSIONS
The circadian HSCs trafficking during steady-state conditions, may promote the maintenance of haematopoiesis through the life of individuals.
Giudice
Aldo
A
Second University of Naples, Department of Biochemistry and Biophysics, Via Costantinopoli 16, 80138 Naples, Italy.
Caraglia
Michele
M
Marra
Monica
M
Montella
Maurizio
M
Maurea
Nicola
N
Abbruzzese
Alberto
A
Arra
Claudio
C
D000818:Animals; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D002940:Circadian Rhythm; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D022702:Receptors, Adrenergic, beta-3 / Q000502:physiology*
D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D022702:Receptors, Adrenergic, beta-3