Hemogenic Endothelium within the Zebrafish Caudal Hematopoietic Tissue illustrates the Common Ties of the Vascular and Hematopoietic Systems

Hemogenic endothelium involves the specification of a hematopoietic stem cell HSC from an existing endothelial cell. It, along with common developmental origins, co-regulation, and shared niches are examples of the close ties the hematopoietic and endothelial lineages share in development. As a significant portion of total HSCs are generated via a hemogenic endothelium intermediate, modulation of this pathway is expected to impact both hematopoietic and endothelial development. Currently, our understanding of how endothelial cells transition to the HSC lineage is still limited. We found that non-aortic endothelial cells, specifically venous endothelial cells, are capable of undergoing the transition to an HSC lineage, suggesting that the hemogenic capacity is a more general characteristic of endothelial cells then previously appreciated. When we analyzed these cells further, we found that they were positive for venous specific markers and well as hematopoietic transcription factors. Further, we identified a potential homolog of Platelet Endothelial Cell Adhesion Molecule 1 PECAM1 in zebrafish and characterized its expression during development. We found that this molecule is expressed in a manner consistent with PECAM1 and is involved in flow-dependent process. Finally, we find that loss of this PECAM1-like molecule is capable of modulating hematopoiesis, suggesting that the vascular and hematopoietic share common machinery responsible for the observed response to blood flow.