Role of angiopoietin-1/Tie2 signaling on endothelial and hematopoietic differentiation of pluripotent stem cell = 다능성 줄기세포의 혈관내피세포 및 혈액세포 분화과정에서 Angiopoietin-1/Tie2 신호전달체계의 역할

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Angiopoietin-1 (Ang1) plays a crucial role in vascular and hematopoietic development mainly through its cognate receptor Tie2. However, little is known about precise role of Ang1 in embryonic stem cell (ESC) differentiation. Here, using soluble and potent variant of Ang1, COMP-Ang1, we determined effect of Ang1 on endothelial and hematopoietic differentiation of mouse ESC in OP9 co-culture system. Strikingly, Ang1 drove endothelial differentiation from $Flk-1^+$ mesodermal progenitor cells, whereas it suppressed hematopoietic differentiation. These effects were mainly mediated through Tie2 signaling, which was evidenced by complete blockade of these effects by soluble Tie2-Fc. The Ang1-induced endothelial differentiation was resulted from enhanced endothelial cell (EC) survival rather than increased EC proliferation. We further determined the effect of Ang1 on $CD41^+$ cells, which were transiently appeared and differentiated into both endothelial and hematopoietic lineages. Intriguingly, Ang1 directed $CD41^+$ cells into endothelial differentiation rather than hematopoietic differentiation. Efficient in vivo neovascularization was obtained with the EC, which were expanded by Ang1 stimulation. In addition, Ang1 also drove endothelial differentiation from mouse induced pluripotent stem cell (iPSC) and human ESC. Taken together, Ang1/Tie2 signaling is a strong stimulator for differentiation and expansion of endothelial linage from ESC and iPSC.
Advisors
Koh, Gou-Youngresearcher고규영researcher
Description
한국과학기술원 : 의과학대학원,
Publisher
한국과학기술원
Issue Date
2011
Identifier
466432/325007  / 020085213
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 의과학대학원, 2011.2, [ v, 100 p. ]

Keywords

embryonic stem cell; endothelial differentiation; Angiopoietin-1; induced pluripotent stem cell; 유도다능성줄기세포; 배아줄기세포; 혈관내피세포분화; 안지오포이에틴-1

URI
http://hdl.handle.net/10203/47185
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=466432&flag=dissertation
Appears in Collection
MSE-Theses_Ph.D.(박사논문)
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