INTERACTION BETWEEN HEMATOPOIETIC STEM CELLS AND ENDOTHELIAL CELlS
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Angiogenesis is closely linked with hematopoiesis, since both have common ancestors; hemangioblasts and they interact with each other. The relationship is reasonable, since vascular and hematopoietic systems must develop together in order to establish the body's oxygen-delivery system during organogenesis. We have shown that the first site where hematopoietic stem cells (HSCs) proliferate is omphalomesenteric artery (OA) besides para-aortic splanchnopleural region (P-Sp). HSCs form aggregates, adhere to ECs and express TIE2/TEK. From P-Sp explants at E8.5-9.5, vascular bed formation (vasculogenesis) and vascular network formation (angiogenesis) are observed in addition to definitive hematopoiesis P-Sp culture from TIE2 deficient embryos revealed that the TIE2 signalling is critic for definitive hematopoiesis as well as angiogenesis. Stimulation of TIE2^+ HSCs in OA by angiopoietin-1 (Ang-1), a ligand for TIE2, promoted the cell adhesion to fibronectin through integrins. These HSCs remarkably proliferated in the presence of Ang-1 and SCF. Interestingly, Ang-1 is selectively expressed on HSCs such as c-Kit^+TIE2^+ cells. It is suggested that autocrine loop of Ang-1 is involved in self-renewing of HSCs. We also show that HSCs e essential for angiogenesis during embryogenesis.
- 日本組織細胞化学会の論文
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