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

Biochem Biophys Res Commun. 2013 Jan 4;430(1):20-5. doi: 10.1016/j.bbrc.2012.11.002. Epub 2012 Nov 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiopoietin-1 / genetics
  • Angiopoietin-1 / metabolism*
  • Animals
  • Blood Vessels / abnormalities
  • Bone Marrow Cells / cytology
  • Cell Lineage*
  • Cell Separation
  • Cells, Cultured
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Embryo Loss / genetics
  • Embryo Loss / metabolism
  • Extracellular Matrix Proteins / metabolism
  • Glycoproteins / metabolism
  • Hematopoiesis*
  • Hematopoietic Stem Cells / cytology*
  • Matrilin Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Osteoblasts / metabolism
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptor, TIE-2
  • Signal Transduction


  • Angiopoietin-1
  • Angpt1 protein, mouse
  • Collagen Type I
  • Extracellular Matrix Proteins
  • Glycoproteins
  • Matn1 protein, mouse
  • Matrilin Proteins
  • Receptor Protein-Tyrosine Kinases
  • Receptor, TIE-2
  • Tek protein, mouse