During ontogenesis and the entire adult life hematopoietic stem and progenitor cells have the capability to migrate. In comparison to the process of peripheral leukocyte migration in inflammatory responses, the molecular and cellular mechanisms governing the migration of these cells remain poorly understood. A common feature of migrating cells is that they need to become polarized before they migrate. Here we have investigated the issue of cell polarity of hematopoietic stem/progenitor cells in detail. We found that human CD34 ؉ hematopoietic cells (1) acquire a polarized cell shape upon cultivation, with the formation of a leading edge at the front pole and a uropod at the rear pole; (2) exhibit an amoeboid movement, which is similar to the one described for migrating peripheral leukocytes; and (3) redistribute several lipid raft markers including cholesterol-binding protein prominin-1 (CD133) in specialized plasma membrane domains. IntroductionDuring ontogenesis the earliest progenitors of the mammalian adult hematopoietic system are initially formed in the intraembryonic aorta-gonad-mesonephros (AGM) and it seems very likely that such AGM-derived hematopoietic stem cells (HSCs) emigrate and colonize the fetal liver, the main site of embryonic hematopoiesis. During neonatal stages, HSCs migrate again; they leave the fetal liver to enter the blood stream and home to the bone marrow (BM), the main side of adult hematopoiesis. 1 More than 30 years of clinical experience as well as several animal models have demonstrated that neonatal and adult HSCs retain their ability to migrate into the BM and the capacity to reconstitute the entire hematopoietic system. 2 It appears that the homing process of transplanted HSCs is based on a naturally occurring process in which adult HSCs and progenitors travel from BM to blood and back to functional niches in BM and maybe into other organs. 3 Remarkably, despite the central role of these phenomena in hematopoietic stem cell biology and their therapeutic relevance, the molecular and cellular mechanisms, which involve chemokines for navigation, and adhesive proteins for interactions, to guide them to their appropriate niche, remain poorly understood. [4][5][6][7][8] In contrast, more is known about the migration process of peripheral leukocytes in inflammatory responses in which they are attracted to leave the blood stream and enter tissues by crossing the vascular endothelium. As reviewed by Sanchez-Madrid and del Pozo, 9 the first requirement for cells that initiate migration is the acquisition of a polarized morphology that enables them to turn intracellularly generated forces into net cell locomotion. In this context it has been shown that chemokines trigger processes that induce changes in the organization of the cytoskeleton, resulting in an observable switch from a spherical into a polarized cell shape. It is established that this polarization requires the activity of phosphoinositol-3-kinase (PI3K), an enzyme involved in signal transduction events. 10,11 Polarized leuko...

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