Adult mammalian hematopoietic stem cells (HSCs) reside in the bone marrow (BM) but can be mobilized into blood for use in transplantation. HSCs interact with BM niche cells that produce growth factor c-Kit ligand (Kitl/SCF) and chemokine CXCL12, and were thought to be static and sessile. We used two-photon laser scanning microscopy to visualize genetically labeled HSCs in the BM of live mice for several hours. The majority of HSCs showed a dynamic non-spherical morphology and significant motility, undergoing slow processive motion interrupted by short stretches of confined motion. HSCs moved in the perivascular space and showed intermittent close contacts with SCF-expressing perivascular stromal cells. In contrast, mobilization-inducing blockade of CXCL12 receptor CXCR4 and integrins rapidly abrogated HSC motility and shape dynamics in real time. Our results reveal an unexpectedly dynamic nature of HSC residence in the BM and interaction with the SCF⁺ stromal niche, which is disrupted during HSC mobilization.

成年哺乳动物造血干细胞 (HSC) 存在于骨髓 (BM) 中，但可以动员到血液中用于移植。HSC 与产生生长因子 c-Kit 配体 (Kit1/SCF) 和趋化因子 CXCL12 的 BM 生态位细胞相互作用，并且被认为是静态和固着的。我们使用双光子激光扫描显微镜观察活小鼠 BM 中基因标记的 HSC 数小时。大多数 HSC 显示出动态的非球形形态和显着的运动性，经历缓慢的连续运动，被短时间的受限运动中断。HSCs 在血管周围空间中移动，并显示出与表达 SCF 的血管周围基质细胞的间歇性密切接触。相比之下，CXCL12 受体 CXCR4 和整合素的动员诱导阻断可实时快速消除 HSC 运动和形状动力学。⁺基质生态位，在 HSC 动员期间被破坏。