A common progenitor for haematopoietic and endothelial lineages in the zebrafish gastrula

Abstract

It has been proposed that haematopoietic and endothelial cells share a common progenitor, termed the haemangioblast. This idea was initially conceived as a result of the observation that these two cell types develop in close proximity to each other within the embryo. Support for this hypothesis was provided by studies on single-cell-derived colonies that can produce both haematopoietic and endothelial cells in vitro. Although these data point towards the existence of a common progenitor for these two lineages, the presence of a bipotential progenitor cell has yet to be demonstrated in vivo. Through the construction of single-cell-resolution fate maps of the zebrafish late blastula and gastrula, we demonstrate that individual cells can give rise to both haematopoietic and endothelial cells. These bipotential progenitors arise along the entire extent of the ventral mesoderm and contribute solely to haematopoietic and endothelial cells. We also find that only a subset of haematopoietic and endothelial cells arise from haemangioblasts. The endothelial descendants of the haemangioblasts all clustered in a specific region of the axial vessels regardless of the location of their progenitors. Our results provide in vivo evidence supporting the existence of the haemangioblast and reveal distinct features of this cell population.

Molecular and developmental biology of the hemangioblast

“…Nevertheless, these studies could not rule out the existence of hemangioblasts in early and middle streak embryos due to the sensitivity of assays they used. Together with the observation in zebrafish embryos (Vogeli et al, 2006), these studies support that a small fraction of endothelial and hematopoietic cells are derived from the hemangioblast and others are independently from mesodermal cells in mouse and zebrafish embryos.…”

“…Therefore, the hemogenic endothelial cells have characteristics of definitive hemangioblasts in late somite stage embryos (Jaffredo et al, 2005;Tavian and Peault, 2005). These early observations in chick, mouse, and human embryos play an important role in the evolution of the hemangioblast concept and the ultimate identification of hemangioblasts in mouse and human ESC-derived embryoid bodies (EBs), and mouse and zebrafish embryos as described below (Choi et al, 1998;Lu et al, 2006;Vogeli et al, 2006;Kennedy et al, 2007).…”

“…This argues that the ventral marginal cells identified by this study are equivalent to hemangioblasts. With the help of newly developed transgenic flk1: EGFP zebrafish for labeling endothelial cells and gata1:dsRed for labeling hematopoietic cells, the Stainier laboratory has now fully taken advantage of this lineage tracing technique and has constructed a single-cell-resolution fate map of the zebrafish late blastula and gastrula (Vogeli et al, 2006). This led to a firm demonstration of the existence of hemangioblasts in the ventral mesoderm of shield-stage embryos.…”

“…By using mouse and human ESC cultures, blast-colonyforming cells (BL-CFCs) are isolated and characterized clonally to produce both endothelial and hematopoietic cells in the presence of vascular endothelial growth factor-A (VEGF-A) and bone morphogenetic protein-4 (BMP4; Choi et al, 1998;Nishikawa et al, 1998;Lu et al, 2006;Kennedy et al, 2007). Fate mapping in the zebrafish gastrula suggests that hemangioblasts are interspersed with hematopoietic and endothelial progenitors in the ventral-lateral mesoderm (Lee et al, 1994;Vogeli et al, 2006). On the other hand, several studies have suggested that endothelial and hematopoietic lineages are independently derived from mesodermal cells (Kinder et al, 1999;Furuta et al, 2006;Vogeli et al, 2006).…”

“…Fate mapping in the zebrafish gastrula suggests that hemangioblasts are interspersed with hematopoietic and endothelial progenitors in the ventral-lateral mesoderm (Lee et al, 1994;Vogeli et al, 2006). On the other hand, several studies have suggested that endothelial and hematopoietic lineages are independently derived from mesodermal cells (Kinder et al, 1999;Furuta et al, 2006;Vogeli et al, 2006). Molecular identity and plasticity of hemangioblasts are not fully characterized.…”