Definitive hematopoietic commitment within the embryonic vascular endothelial-cadherin(+) population

Area of Science:

• Developmental Biology
• Hematopoiesis
• Stem Cell Biology

Background:

• Hematopoietic stem cells (HSCs) are crucial for lifelong blood production.
• Identifying early embryonic precursors for hematopoiesis is key to understanding blood development.
• Vascular endothelial (VE)-cadherin is a marker expressed on endothelial cells and some hematopoietic precursors.

Purpose of the Study:

• To evaluate the hematopoietic potential of FLK1(+) and VE-cadherin(+) cells from embryonic development.
• To determine the capacity of these cells to generate hematopoietic cells ex vivo.
• To assess their contribution to the hematopoietic system of recipient mice.

Main Methods:

• Isolation of FLK1(+) and VE-cadherin(+) cells from 7.5- to 9.5-day post-coitum (dpc) concepti.
• Ex vivo culture of these cells on OP9 stromal cells.
• Intrahepatic injection of VE-cadherin(+)CD45(-) cells into busulfan-treated SCID recipients.
• Monitoring of hematopoietic development and engraftment.

Main Results:

• VE-cadherin(+) cells from 7.5- and 8.5-dpc concepti showed greater hematopoietic potential ex vivo than FLK1(+) VE-cadherin(-) cells.
• VE-cadherin(+) cells from the 8.5-dpc yolk sac also exhibited significant hematopoietic potential.
• Intrahepatic injection of VE-cadherin(+)CD45(-) cells led to long-term lymphoid system engraftment in SCID recipients.

Conclusions:

• VE-cadherin(+) cells, particularly from early embryonic stages, are effective precursors for hematopoietic cell generation.
• Cells with an endothelial phenotype (VE-cadherin(+)) can generate long-term hematopoietic precursors.
• FLK1(+)VE-cadherin(-) cells, potentially lateral plate mesoderm, are less effective hematopoietic progenitors compared to VE-cadherin(+) cells.