Second University of Naples, Department of Biochemistry and Biophysics, Via Costantinopoli 16, 80138 Naples, Italy.
Expert Opin Ther Targets. 2010 May;14(5):567-75. doi: 10.1517/14728221003769887.
Under homeostasis, small numbers of haematopoietic stem cells (HSCs) are detectable in the bloodstream of mammals, but the mechanisms of their trafficking are unknown.
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.
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.
The circadian HSCs trafficking during steady-state conditions, may promote the maintenance of haematopoiesis through the life of individuals.
在体内平衡状态下,哺乳动物的血液中可检测到少量造血干细胞(HSCs),但其运输机制尚不清楚。
研究表明,由于 12 小时光照/12 小时黑暗的标准周期,循环 HSCs 表现出明显的昼夜波动。当小鼠连续两周接受光照或出现时差时,昼夜循环 HSCs 波动会强烈改变。此外,循环 HSCs 的波动与骨髓微环境中趋化因子 CXCL12 的表达呈反相波动。昼夜循环 HSC 运输和 CXCL12 的表达受中央时钟的核心基因调节,通过来自骨髓交感神经系统(SNS)神经末梢的肾上腺素能激素的节律性分泌。
本篇综述总结了最近关于 HSC 在骨髓中释放的昼夜调节的发现,检查了中央分子钟通过节律性分泌肾上腺素能激素调节骨髓基质细胞中 CXCL12 的分子机制,这些激素通过 SNS 的神经末梢在骨髓中局部传递。
在稳态条件下,昼夜循环 HSCs 的运输可能通过个体的生命来促进造血的维持。