In mammals, during definitive hematopoiesis, all blood, composed of a diverse population of white blood cells (monocytes, granulocytes and lymphocytes), red blood cells (erythrocytes), and platelets (thrombocytes), is thought to derive from a common progenitor termed the hematopoietic stem cell ( Graf, 2008 Orkin and Zon, 2008 Reya et al., 2001). Hence where a cell is produced, and not just when, often defines whether it is considered primitive or definitive. One of the hallmarks of vertebrate hematopoiesis is that blood cells are produced in ever changing sites throughout development ( Baron, 2003 Keller et al., 1999 Lacaud et al., 2001 Orkin and Zon, 2008). Hematopoiesis in vertebrates occurs in two successive waves known as primitive (embryonic) and definitive (adult) (reviewed in: Godin and Cumano 2002). Our results demonstrate the existence of primitive hematopoietic progenitors that are segregated very early in development and that are specified to produce either a unipotent or a multipotent blood cell lineage. In contrast, on the ventral gastrula, blood progenitors are multipotential cells with rapid cell cycles, populate the intermediate cell mass (ICM), and differentiate into erythrocytes, neutrophils, and thrombocytes. On the dorsal gastrula, blood progenitors are unipotential cells that divide infrequently, populate the rostral blood islands (RBI), and differentiate into macrophages. Using a variety of in vivo celltracing techniques, we show that primitive blood in zebrafish derives from two different progenitor types. While definitive hematopoiesis may produce many diverse blood types via a common multipotent progenitor, primitive hematopoiesis has been thought to produce only erythrocytes or macrophages via progenitors that are unipotent for single blood lineages. Vertebrate hematopoiesis first produces primitive (embryonic) lineages and ultimately generates the definitive (adult) blood.
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