**5. Endothelial-related markers**

Hematopoietic cells are thought to originate from the hemangioblast and/or the hemogenic endothelium, which can produce hematopoietic cells and endothelial cells. Therefore, it seems quite natural that HSC share some surface molecules with the endothelial lineage. CD34, PECAM-1/CD31, endoglin, Tie2 and VE-cadherin are well-known endothelial antigens that also mark HSC particularly at early developmental stages (Mikkola & Orkin 2006; Takakura et al., 1998; Yokota et al, 2006). In addition, recent studies have identified endomucin, endothelial protein-C receptor/CD201, and junctional adhesion molecule-A that are common to HSC and endothelial cells (Matsubara et al., 2005; Balazs et al., 2006; Sugano et al., 2008). Although, as discussed above, the expression level of some of these antigens declines or even diminishes at later stages of development (Mikkola & Orkin 2006), each of these advances offered the promise of learning more about how HSC arise de novo and function throughout life. It is crucial to define the means to identify the authentic HSC at all developmental stages so that we can ultimately understand the precise molecular mechanisms of the HSC development.

Markers for Hematopoietic Stem Cells: Histories and Recent Achievements 83

(A) Flow cytometry analysis was performed for mouse E14.5 fetal liver cells using anti-c-kit, anti- Sca1,

subjected to methylcellulose colony formation assay. Numbers of CFUs (B) and morphology of the

Fig. 1. ESAM expression on the HSC-enriched population of mouse fetal liver

ckitHi Sca1+ fraction were sorted and

and anti-ESAM Abs. ESAM-/Lo or ESAMHi cells of the Rag1/GFP-

colonies (C) are shown. (Modified from reference Yokota et al., 2009)
