Transdifferentiation of hematopoietic stem cells and endothelial progenitors

造血干细胞和内皮祖细胞的转分化

• 批准号: 14207042
• 负责人: OIKE Yuichi
• 金额: $ 32.61万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14207042/
• 关键词: anegiopoietin; Angptl; TIE2; bone marrow; stem cell niche; osteoblast; angiogenesis; metabolism; 酸化ストレス; リンパ管新生; ATM; 幹細胞分化転換; 造血幹細胞; 血管幹細胞; AML1; ES細胞; Side Population; Hemangioblast; Tie2受容体

In this project, we try to clarify the differentiation pathway to hematopoietic stem cells (HSCs) and vascular endothelial cells from common progenitor cells or hemangioblasts. Hemogenic endothelial cells were defined in dorsal aorta in embryos, while hemangioblasts were not clarified yet at a clonal level in adult bone marrow. Both HSCs and endothelial cells express common surface molecules, CD31, CD34, Flk-1 and Tie2, which is a receptor for angiopoietins (Angs).1)We have demonstrated that Tie2-positive HSCs adhere to Ang-1-producing osteoblasts, and that this signal is critical for maintaining the quiescent stem cells (Cell, 2004).2)Angiopoietin-like proteins (Angptl) 1 and 2 synergistically show the anti-apoptotic effects on vascular endothelial cells using a Morpholino in Zebrafish.3)Surprisingly, Angplt 6 is involved in the energy metabolism as well as angiogenesis. Angptl 6 KO mice show the obesity, while Tg mice show some resistance to obesity and diabetes (Nat.Med.2005).

在本项目中，我们试图阐明从普通祖细胞或血管母细胞向造血干细胞(HSCs)和血管内皮细胞分化的途径。胚胎的背主动脉内有血源性内皮细胞的存在，而成人骨髓中的血管母细胞尚未在克隆水平上被明确。造血干细胞和血管内皮细胞都表达共同的表面分子CD31、CD34、Flk-1和血管生成素受体Tie2。1)我们已经证明Tie2阳性的HSC与产生Ang-1的成骨细胞黏附，并且这个信号对维持静止的干细胞至关重要(Cell，2004)。2)血管生成素样蛋白(Angptl)1和2协同发挥抗血管内皮细胞凋亡的作用。Angptl 6 KO小鼠表现出肥胖，而TG小鼠表现出对肥胖和糖尿病的一些抵抗力(Nat.Med.2005)。

项目成果

Yamada Y, et al.: "Neuropilin-1 on hematopoietic cells as a source of vascular development."Blood. 101. 1801-1809 (2003)

Yamada Y 等人：“造血细胞上的 Neuropilin-1 作为血管发育的来源。”血液。

Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells

• DOI: 10.1038/nature02989
• 发表时间: 2004-10-21
• 期刊: NATURE
• 影响因子: 64.8
• 作者: Ito, K;Hirao, A;Suda, T
• 通讯作者: Suda, T

Mesenchymal stem cells in perichondrium express activated leukocyte cell adhesion molecule and participate in bone marrow formation

• DOI: 10.1084/jem.20011700
• 发表时间: 2002-06-17
• 期刊: JOURNAL OF EXPERIMENTAL MEDICINE
• 影响因子: 15.3
• 作者: Arai, F;Ohneda, O;Suda, T
• 通讯作者: Suda, T

Tie2/Angiopoietin-1 signaling regulates quiescence of hematopoietic stem cells in a niche.

Tie2/Angiopoietin-1 信号传导调节微环境中造血干细胞的静止。

• 发表时间: 2004
• 期刊: Cell 118
• 作者: Arai F;et al.
• 通讯作者: et al.

Regulation of vasculogenesis and angiogenesis by EphB/ephrin-B2 signaling between endothelial cells and surrounding mesenchymal cells

• DOI: 10.1182/blood.v100.4.1326.h81602001326_1326_1333
• 发表时间: 2002-08-15
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Oike, Y;Ito, Y;Suda, T
• 通讯作者: Suda, T