Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Laboratory of Chronopharmacology, Department of Physiology, Institute of Bioscience, University of São Paulo, São Paulo, Brazil.
Exp Hematol. 2019 Oct;78:1-10. doi: 10.1016/j.exphem.2019.08.008. Epub 2019 Sep 5.
Hematopoietic stem and progenitor cells (HSPCs) are essential for daily mature blood cell production, host immunity, and osteoclast-mediated bone turnover. The timing at which stem cells give rise to mature blood and immune cells while maintaining the bone marrow (BM) reservoir of undifferentiated HSPCs and how these opposite tasks are synchronized are poorly understood. Previous studies revealed that daily light onset activates norepinephrine (NE)-induced BM CXCL12 downregulation, followed by CXCR4 HSPC release to the circulation. Recently, we reported that daily light onset induces transient elevations of BM NE and tumor necrosis factor (TNF), which metabolically program BM HSPC differentiation and recruitment to replenish the blood. In contrast, darkness onset induces lower elevations of BM NE and TNF, activating melatonin production, which metabolically reprograms HSPCs, increasing their short- and long-term repopulation potential, and BM maintenance. How the functions of BM-retained HSPCs are influenced by daily light and darkness cycles and their clinical potential are further discussed.
造血干细胞和祖细胞（HSPCs）对于日常成熟血细胞的产生、宿主免疫和破骨细胞介导的骨转换至关重要。干细胞在产生成熟的血液和免疫细胞的同时，如何维持骨髓（BM）中未分化 HSPC 的储存库，以及如何同步这些相反的任务，目前了解甚少。先前的研究表明，每日光照开始时会激活去甲肾上腺素（NE）诱导的 BM CXCL12 下调，随后 CXCR4 HSPC 释放到循环中。最近，我们报道称，每日光照开始时会导致 BM NE 和肿瘤坏死因子（TNF）的短暂升高，从而代谢性地规划 BM HSPC 分化和募集以补充血液。相比之下，黑暗开始时会引起 BM NE 和 TNF 的较低升高，从而激活褪黑素的产生，这会代谢性地重新编程 HSPC，增加其短期和长期的再殖能力，并维持 BM。进一步讨论了 BM 中保留的 HSPC 的功能如何受到每日光照和黑暗周期的影响及其临床潜力。
