Enhanced Angpt1/Tie2 signaling affects the differentiation and long-term repopulation ability of hematopoietic stem cells |
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| Authors: | Yoshiko Matsumoto Ikushima Fumio Arai Yuka Nakamura Kentaro Hosokawa Yoshiaki Kubota Masanori Hirashima Hirofumi Toyama Toshio Suda |
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| Institution: | 1. Department of Histopathology, St James''s Hospital, Dublin, Ireland;2. Department of Histopathology and Morbid Anatomy, Trinity College, Dublin, Ireland;1. Faculty of Pharmacy, Takasaki University of Health and Welfare, Takasaki, Japan;2. Department of Drug Absorption and Pharmacokinetics, Tohoku Pharmaceutical University, Sendai, Japan |
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| Abstract: | 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. |
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