Lucas Daniel, Battista Michela, Shi Patricia A, Isola Luis, Frenette Paul S
Cell Stem Cell. 2008 Oct 9;3(4):364-6. doi: 10.1016/j.stem.2008.09.004.
Endogenous rhythmicity likely evolved as a mechanism allowing organisms to anticipate predictable daily changes in the environment (Rutter et al., 2002). Under homeostasis, murine hematopoietic stem cell (HSC) egress is orchestrated by rhythmic beta 3 adrenergic signals delivered by the sympathetic nervous system (SNS) that regulate Cxcl12 expression in stromal cells (Mendez-Ferrer et al., 2008). Here, we show that CXCR4 is also regulated under circadian control whose rhythm is synchronized with its ligand, CXCL12, to optimize HSC trafficking. These circadian oscillations are inverted in humans compared to the mouse and continue to influence the yield even when stem cell mobilization is enforced. Our results suggest that the human HSC yield for clinical transplantation might be significantly greater if patients were harvested during the evening compared to the morning.
内源性节律可能是作为一种机制进化而来的，该机制使生物体能够预测环境中可预测的每日变化（Rutter等人，2002年）。在稳态下，小鼠造血干细胞（HSC）的流出由交感神经系统（SNS）传递的节律性β3肾上腺素能信号精心安排，该信号调节基质细胞中Cxcl12的表达（Mendez-Ferrer等人，2008年）。在这里，我们表明CXCR4也受昼夜节律控制，其节律与其配体CXCL12同步，以优化HSC运输。与小鼠相比，人类的这些昼夜节律振荡是相反的，并且即使在强制进行干细胞动员时，这些节律仍会影响产量。我们的结果表明，如果在晚上而不是早上采集患者的样本，那么用于临床移植的人类HSC产量可能会显著更高。
