Lineage analysis of the hemangioblast as defined by FLK1 and SCL expression

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Abstract
Accumulating studies support the idea that a common progenitor, termed the hemangioblast, generates both hematopoietic and endothelial cell lineages. To better define the relationship between these cell lineages, we have generated knock-in embryonic stem (ES) cells carrying a non-functional human CD4 at the Scl locus. By using in vitro differentiated Scl+/CD4 ES cells, we demonstrate that FLK1 and SCL are molecular determinants of the hemangioblast. Furthermore, our studies demonstrate that hematopoietic and endothelial cells develop via distinct, sequential generation of FLK1 and SCL-expressing cells. FLK1+CD4- cells first arise in developing embryoid bodies. The Scl gene is turned on within FLK1+CD4- cells to give rise to FLK1+CD4+ cells. Alternatively, a subpopulation of the initial FLK1+CD4- cells remains as SCL negative. Within the FLK1+CD4+ cells, FLK1 is down regulated to generate FILK1-CD4+ cells. Replating studies demonstrate that hematopoietic progenitors are enriched within FLK1+CD4+ and FLK1-CD4+ cells, while endothelial cells develop from FLK1+CD4+ and FLK1+CD4- cell populations.