Enhanced Angpt1/Tie2 signaling affects the differentiation and long-term repopulation ability of hematopoietic stem cells

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• 作者：Yoshiko Matsumoto Ikushima^a ; ^b ; ¹ ; Fumio Arai^a ; ¹ ; ^{farai@sc.itc.keio.ac.jp} ; Yuka Nakamura^c ; Kentaro Hosokawa^a ; Yoshiaki Kubota^a ; Masanori Hirashima^d ; Hirofumi Toyama^a ; Toshio Suda^a ; ^{sudato@z3.keio.jp}
• 关键词：Angpt1 ; angiopoietin1 ; Tie2 ; tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 2
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2013
• 出版时间：4 January, 2013
• 年：2013
• 卷：430
• 期：1
• 页码：20-25
• 全文大小：413 K

文摘

Angiopoietin-1 (Angpt1) signaling via the Tie2 receptor regulates vascular and hematopoietic systems. To investigate the role of Angpt1-Tie2 signaling in hematopoiesis, we prepared conditionally inducible transgenic (Tg) mice expressing a genetically engineered Angpt1, cartridge oligomeric matrix protein (COMP)-Angpt1. The effects of COMP-Angpt1 overexpression in osteoblasts on hematopoiesis were then investigated by crossing COMP-Angpt1 Tg mice with Col1a1-Cre Tg mice. Interestingly, peripheral blood analyses showed that 4 week (wk)-old (but not 8 wk-old) Col1a1-Cre+/COMP-Angpt1+ mice had a lower percentage of circulating B cells and a higher percentage of myeloid cells than Col1a1-Cre?/COMP-Angpt1+ (control) mice. Although there were no significant differences in the immunophenotypic hematopoietic stem and progenitor cell (HSPC) populations between Col1a1-Cre+/COMP-Angpt1+ and control mice, lineage^?Sca-1⁺c-Kit⁺ (LSK) cells isolated from 8 wk-old Col1a1-Cre+/COMP-Angpt1+ mice showed better long-term bone marrow reconstitution ability. These data indicate that Angpt1-Tie2 signaling affects the differentiation capacity of hematopoietic lineages during development and increases the stem cell activity of HSCs.