한빛사논문
- 조회2,579
Abstract
Hyung Joon Joo1, Honsoul Kim1, Sang-Wook Park1, Hyun-Jai Cho2, Hyo-Soo Kim2, Do-Sun Lim3, Hyung-Min Chung4, Injune Kim1, Yong-Mahn Han1, and Gou Young Koh1,*
1 Laboratory for Vascular Biology and Stem Cell, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea, Republic of;
2 National Research Laboratory for Cardiovascular Stem Cell, Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea, Republic of;
3 Department of Cardiology, College of Medicine, Korea University, Seoul, Korea, Republic of;
4 Stem Cell Research Laboratory, CHA Stem Cell Institute, Pochon CHA University, Seoul, Korea, Republic of
* Corresponding author
Abstract
Angiopoietin-1 (Ang1) plays a crucial role in vascular and hematopoietic development mainly through its cognate receptor Tie2. However, little is known about the precise role of Ang1 on embryonic stem cell (ESC) differentiation. Here, using COMP-Ang1 (soluble and potent variant of Ang1), we explored the effect of Ang1 on endothelial and hematopoietic differentiation of mouse ESCs in OP9 co-culture system. Ang1 promoted endothelial cell (EC) differentiation from Flk-1+ mesodermal precursors. This effect mainly occurred through Tie2 signaling, but was interfered in the presence of soluble Tie2-Fc. We accounted for this Ang1 induced expansion of ECs by enhanced proliferation and survival. Ang1 also had effect on CD41+ cells, which are transient precursors that can differentiate into both endothelial and hematopoietic lineages. Intriguingly, Ang1 drove to induce the preferential differentiation of CD41+ cells toward ECs instead of hematopoietic cells. The promoted EC expansion by Ang1 was also recapitulated in induced pluripotent stem cells (iPSCs) and human ESCs. Transplantation of ECs obtained from Ang1 stimulated ESC into mice successfully achieved in vivo neovascularization. Taken together, Ang1/Tie2 signaling has a pivotal role on ESC-EC differentiation, and this effect of Ang1 can be exploited to expand EC populations.
논문정보
- Research article
- 2011년 06월 (BRIC 등록일 )
- 국내 연구진
- 의약학 > 재생의학
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