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. genesis 48:563–567, 2010. © 2010 Wiley‐Liss, Inc.

[1]  Jian Yang,et al.  Restoration of Runx1 Expression in the Tie2 Cell Compartment Rescues Definitive Hematopoietic Stem Cells and Extends Life of Runx1 Knockout Animals Until Birth , 2009, Stem cells.

[2]  Shin-Ichi Nishikawa,et al.  Continuous single-cell imaging of blood generation from haemogenic endothelium , 2009, Nature.

[3]  Georges Lacaud,et al.  The haemangioblast generates haematopoietic cells through a haemogenic endothelium stage , 2009, Nature.

[4]  Kyunghee Choi,et al.  Both primitive and definitive blood cells are derived from Flk-1+ mesoderm. , 2009, Blood.

[5]  Elaine Dzierzak,et al.  Runx1 is required for the endothelial to hematopoietic cell transition but not thereafter , 2009, Nature.

[6]  Michael S. Becker,et al.  Fate tracing reveals the endothelial origin of hematopoietic stem cells. , 2008, Cell stem cell.

[7]  K. McGrath,et al.  All primitive and definitive hematopoietic progenitor cells emerging before E10 in the mouse embryo are products of the yolk sac. , 2008, Blood.

[8]  S. Nishikawa,et al.  Cell tracing shows the contribution of the yolk sac to adult haematopoiesis , 2007, Nature.

[9]  Satoru Takahashi,et al.  Primitive erythropoiesis from mesodermal precursors expressing VE-cadherin, PECAM-1, Tie2, endoglin, and CD34 in the mouse embryo. , 2006, Blood.

[10]  K. McGrath,et al.  Hematopoiesis in the yolk sac: more than meets the eye. , 2005, Experimental hematology.

[11]  A. Bernstein,et al.  Requirement for the TIE family of receptor tyrosine kinases in adult but not fetal hematopoiesis , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Rainer Constien,et al.  Temporal Cre‐mediated recombination exclusively in endothelial cells using Tie2 regulatory elements , 2002, Genesis.

[13]  A. Koniski,et al.  Spatial and temporal emergence of high proliferative potential hematopoietic precursors during murine embryogenesis , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[14]  R. Hammer,et al.  Tie2-Cre transgenic mice: a new model for endothelial cell-lineage analysis in vivo. , 2001, Developmental biology.

[15]  G. Yancopoulos,et al.  Critical role of the TIE2 endothelial cell receptor in the development of definitive hematopoiesis. , 1998, Immunity.

[16]  Thomas N. Sato,et al.  Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation , 1995, Nature.

[17]  M. Gertsenstein,et al.  Dominant-negative and targeted null mutations in the endothelial receptor tyrosine kinase, tek, reveal a critical role in vasculogenesis of the embryo. , 1994, Genes & development.