Submitted March 27, 2006
Accepted August 6, 2006
Primitive erythropoiesis from mesodermal precursors expressing VE-cadherin, PECAM-1, Tie2, endoglin and CD34 in the mouse embryo
Masatsugu Ema*, Tomomasa Yokomizo, Asami Wakamatsu, Tsumoru Terunuma, Masayuki Yamamoto, and Satoru Takahashi
Graduate School of Comprehensive Human Sciences, University of Tsukuba, Japan
Center for TARA, The University of Tsukuba, Japan
* Corresponding author; email: masaema{at}md.tsukuba.ac.jp.
Vascular endothelial (VE) cadherin, PECAM-1 (Platelet Endothelial cell adhesion molecule-1), Tie2, CD34 and Endoglin are established markers for adult and embryonic endothelial cells (ECs). Here, we report that the expression of these EC markers is initiated in the extraembryonic region at the late-streak stage (nominal stage E6.75). Immunohistochemical analysis shows that EC marker-positive cells arise in a subset of Flk1 (VEGF-R2) mesodermal cells. In contrast, GATA1, a marker for primitive erythropoietic progenitors, is expressed in a more restricted subset of Flk1-positive cells. Using flow cytometry, we observed that the GATA1-positive cell population existed as a subset of the EC marker-positive cell. Consistent with this notion, we showed that primitive erythropoietic progenitors are enriched in PECAM-1- and Tie2-positive cells using the primitive hematopoietic colony assay. These results suggest that primitive hematopoietic cells arise from EC marker-positive cells. Thus, VE-cadherin, PECAM-1, CD34, Endoglin and Tie2 are not only expressed in adult and embryonic ECs, but also in extraembryonic Flk1-positive cells during gastrulation. The latter cell population includes progenitors giving rise to primitive hematopoietic cells, suggesting that both primitive and definitive hematopoietic cells in the mouse embryo arise from EC marker-positive cells.