Dynamic Cross Talk between S1P and CXCL12 Regulates Hematopoietic Stem Cells Migration, Development and Bone Remodeling.
Dynamic Cross Talk between S1P and CXCL12 Regulates Hematopoietic Stem Cells Migration, Development and Bone Remodeling.
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DOI：
10.3390/ph6091145
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发表时间：
2013-09-23
期刊：
影响因子：
--
通讯作者：
Lapidot T
中科院分区：
文献类型：
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作者：
Golan K;Kollet O;Lapidot T
造血干细胞（HSC）大多以静止的非运动模式保留在它们的骨髓（BM）小生境中，转变为迁移循环和分化状态，以根据需要用成熟的白细胞补充血液。主要在BM中的主要化学引诱物CXCL 12和主要在血液中的S1 P之间的平衡动态地调节HSC向循环的募集相对于它们在BM中的保留。在警报情况下，应激信号诱导BM中CXCL 12水平降低，而S1 P水平在循环中快速且短暂地增加，从而有利于干细胞动员作为宿主防御和修复机制的一部分。骨髓细胞因子，包括G-CSF，通过PI 3 K途径上调BM中的S1 P信号传导。通过活性氧（ROS）产生诱导基质细胞分泌CXCL 12，并增加HSC中S1 P1表达和ROS信号传导，所有这些都有助于动员。骨转换也受到CXCL 12和S1 P的调节，调节动态BM基质微环境、破骨细胞和干细胞龛，它们都在功能上表达CXCL 12和S1 P受体。总体而言，BM和循环中的CXCL 12和S1 P水平同步，以在稳态和应激情况下相互控制HSC运动性、白细胞产生和破骨细胞/成骨细胞骨转换。
Hematopoietic stem cells (HSCs) are mostly retained in a quiescent non-motile mode in their bone marrow (BM) niches, shifting to a migratory cycling and differentiating state to replenish the blood with mature leukocytes on demand. The balance between the major chemo-attractants CXCL12, predominantly in the BM, and S1P, mainly in the blood, dynamically regulates HSC recruitment to the circulation versus their retention in the BM. During alarm situations, stress-signals induce a decrease in CXCL12 levels in the BM, while S1P levels are rapidly and transiently increased in the circulation, thus favoring mobilization of stem cells as part of host defense and repair mechanisms. Myeloid cytokines, including G-CSF, up-regulate S1P signaling in the BM via the PI3K pathway. Induced CXCL12 secretion from stromal cells via reactive oxygen species (ROS) generation and increased S1P1 expression and ROS signaling in HSCs, all facilitate mobilization. Bone turnover is also modulated by both CXCL12 and S1P, regulating the dynamic BM stromal microenvironment, osteoclasts and stem cell niches which all functionally express CXCL12 and S1P receptors. Overall, CXCL12 and S1P levels in the BM and circulation are synchronized to mutually control HSC motility, leukocyte production and osteoclast/osteoblast bone turnover during homeostasis and stress situations.