The contribution of the Tie2+ lineage to primitive and definitive hematopoietic cells

The regulatory elements of the Tie2/Tek promoter are commonly used in mouse models to direct transgene expression to endothelial cells. Tunica intima endothelial kinase 2 (Tie2) is also expressed in hematopoietic cells, although this has not been fully characterized. We determine the lineages of adult hematopoietic cells derived from Tie2-expressing populations using Tie2-Cre;Rosa26R-EYFP mice. In Tie2-Cre;Rosa26R-EYFP mice, analysis of bone marrow cells showed Cre-mediated recombination in 85% of the population. In adult bone marrow and spleen, we analyzed subclasses of early hematopoietic progenitors, T cells, monocytes, granulocytes, and B cells. We found that ∼ 84% of each lineage was EYFP(+), and nearly all cells that come from Tie2-expressing lineages are CD45(+), confirming widespread contribution to definitive hematopoietic cells. In addition, more than 82% of blood cells within the embryonic yolk sac were of Tie2(+) origin. Our findings of high levels of Tie2-Cre recombination in the hematopoietic lineage have implications for the use of the Tie2-Cre mouse as a lineage-restricted driver strain.