Mice lacking the 4th-group paralog Hoxd4 display malformations of the anterior vertebral column, but are viable and fertile. Here, we report that zebrafish embryos having decreased function of the orthologous hoxd4a gene manifest striking perturbations in vasculogenesis, angiogenesis and primitive and definitive hematopoiesis. These defects are preceded by reduced expression of the hemangioblas...

The fetal liver kinase 1 (FLK-1)(+) hemangioblast can generate hematopoietic, endothelial, and smooth muscle cells (SMCs). ER71/ETV2, GATA2, and SCL form a core transcriptional network in hemangioblast development. Transient coexpression of these three factors during mesoderm formation stage in mouse embryonic stem cells (ESCs) robustly enhanced hemangioblast generation by activating bone morph...

Postnatal CD34(+) cells expressing vascular endothelial growth factor receptor 2 (KDR) generate hematopoietic or endothelial progeny in different in vitro and in vivo assays. Hypothetically, CD34(+)KDR(+) cells may comprise hemangioblasts bipotent for both lineages. This hypothesis is consistent with 2 series of experiments. In the first series, in clonogenic culture permissive for hematopoieti...

Hematopoietic and endothelial cells develop from a common progenitor, the hemangioblast, or directly from mesodermal cells. The molecular pathway that regulates the specification of both cell lineages remains elusive. Here, we show that a lysocardiolipin acyltransferase, lycat, is critical for the establishment of both hematopoietic and endothelial lineages. We isolated lycat from the deletion ...

Primitive erythropoiesis follows a stereotypic developmental program of mesoderm ventralization and internalization, hemangioblast formation and migration, and erythroid lineage specification. Induction of erythropoiesis is inefficient in either ES/iPS cells in vitro or nonhemangioblast cell populations in vivo. Using the chick model, we report that epiblast cells can be directly and efficientl...

Molecular mechanisms that regulate the generation of hematopoietic and endothelial cells from mesoderm are poorly understood. To define the underlying mechanisms, we compared gene expression profiles between embryonic stem (ES) cell-derived hemangioblasts (Blast-Colony-Forming Cells, BL-CFCs) and their differentiated progeny, Blast cells. Bioinformatic analysis indicated that BL-CFCs resembled ...