TY - JOUR
T1 - Enhanced Angpt1/Tie2 signaling affects the differentiation and long-term repopulation ability of hematopoietic stem cells
AU - Ikushima, Yoshiko Matsumoto
AU - Arai, Fumio
AU - Nakamura, Yuka
AU - Hosokawa, Kentaro
AU - Kubota, Yoshiaki
AU - Hirashima, Masanori
AU - Toyama, Hirofumi
AU - Suda, Toshio
N1 - Funding Information:
We sincerely thank Drs. Klaus Rajewsky (Harvard Medical School, Cambridge, MA, USA) and Takeshi Miyamoto (Keio University, Tokyo, Japan) for providing the Mx1-Cre and Col1a1-Cre mice, respectively. This work was supported by the Funding Program for Next Generation World-Leading Researchers (NEXT Program) and a Grant-in-Aid from the Japan Society for the Promotion of Science .
PY - 2013/1/4
Y1 - 2013/1/4
N2 - 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 4week (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.
AB - 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 4week (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.
KW - Angiopoietin1
KW - COMP-Angiopoietin1
KW - Hematopoietic stem cells
KW - Tie2
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U2 - 10.1016/j.bbrc.2012.11.002
DO - 10.1016/j.bbrc.2012.11.002
M3 - Article
C2 - 23149415
AN - SCOPUS:84872371868
SN - 0006-291X
VL - 430
SP - 20
EP - 25
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -