The hemangioblast: from concept to authentication.

The hemangioblast hypothesis has been hotly debated for over a century. Hemangioblasts are defined as multipotent cells that can give rise to both hematopoietic cells and endothelial cells. The existence of hemangioblasts has now been confirmed and many important molecules and several signaling pathways are involved in their generation and differentiation. Fibroblast growth factor, renin-angiotensin system and runt-related transcription factor 1 (Runx1) direct the formation of hemangioblasts through highly selective gene expression patterns. On the other hand, the hemogenic endothelium theory and a newly discovered pattern of hematopoietic/endothelial differentiation make the genesis of hemangioblasts more complicated. But how hemangioblasts are formed and how hematopoietic cells or endothelial cells are derived from remains largely unknown. Here we summarize the current knowledge of the signaling pathways and molecules involved in hemangioblast development and suggest some future clinical applications.