Hemogenic endothelium: origins, regulation, and implications for vascular biology. Semin Cell Dev Biol
ABSTRACT The study of endothelial development has been intertwined with hematopoiesis since the early 20th century when a bi-potential cell (hemangioblast) was noted to produce both endothelial and hematopoietic cells. Since then, ideas regarding the nature of connection between the vascular and hematopoietic systems have ranged from a tenuous association to direct lineage origination. In this review, historical data that spans hematopoietic development is examined within the context of hemogenic endothelium. Hemogenic endothelium, a specialized endothelial population capable of hematopoiesis, is an emerging theory that has recently gained momentum. Evidence across species and decades are reviewed, as are the possible modulators of the phenomenon, which include pathways that specify definitive hematopoiesis (Runx1), arterial identity (Notch1), as well as physiological and developmental factors.
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- "Regulation of the endothelial and hematopoietic lineage specification has stimulated intense interest (Chen et al., 2009; Eilken et al., 2009; Hirschi, 2012; Lancrin et al., 2009). A number of transcription factors and signaling pathways have been reported to play important roles in the regulation of endothelial and hematopoietic mesodermal progenitors (Zape and Zovein, 2011). GATA transcription factors are characterized as having a conserved dual zinc finger domain. "
ABSTRACT: Regulatory mechanisms that govern lineage specification of the mesodermal progenitors to become endothelial and hematopoietic cells remain an area of intense interest. Both Ets and Gata factors have been shown to have important roles in the transcriptional regulation in endothelial and hematopoietic cells. We previously reported Etv2 as an essential regulator of vasculogenesis and hematopoiesis. In the present study, we demonstrate that Gata2 is co-expressed and interacts with Etv2 in the endothelial and hematopoietic cells in the early stages of embryogenesis. Our studies reveal that Etv2 interacts with Gata2 in vitro and in vivo. The protein-protein interaction between Etv2 and Gata2 is mediated by the Ets and Gata domains. Using the embryoid body differentiation system, we demonstrate that co-expression of Gata2 augments the activity of Etv2 in promoting endothelial and hematopoietic lineage differentiation. We also identify Spi1 as a common downstream target gene of Etv2 and Gata2. We provide evidence that Etv2 and Gata2 bind to the Spi1 promoter in vitro and in vivo. In summary, we propose that Gata2 functions as a cofactor of Etv2 in the transcriptional regulation of mesodermal progenitors during embryogenesis.Developmental Biology 05/2014; 389(2). DOI:10.1016/j.ydbio.2014.02.018 · 3.64 Impact Factor
Article: Blood and Lymphatic Vessel Formation[Show abstract] [Hide abstract]
ABSTRACT: Blood and lymphatic vessels deliver oxygen and nutrients, remove waste and CO2, and regulate interstitial pressure in tissues and organs. These vessels begin life early in embryogenesis using transcription factors and signaling pathways that regulate differentiation, morphogenesis, and proliferation. Here we describe how these vessels develop in the mouse embryo, and the signals that are important to their development. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.Cold Spring Harbor perspectives in biology 03/2015; 7(3). DOI:10.1101/cshperspect.a008268 · 8.23 Impact Factor
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ABSTRACT: Diverse subsets of endothelial progenitor cells (EPCs) are used for the treatment of ischemic diseases in clinical trials, and circulating EPCs levels are considered as biomarkers for coronary and peripheral artery disease. However, despite significant steps forward in defining their potential for both therapeutic and diagnostic purposes, further progress has been mired by unresolved questions around the definition and the mechanism of action of EPCs. Diverse culturing methods and detection of various combinations of different surface antigens were used to enrich and identify EPCs. These attempts were particularly challenged by the close relationship and overlapping markers of the endothelial and hematopoietic lineages. This article will critically review the most commonly used protocols to define EPCs by culture assays or by fluorescence-activated cell sorter in the context of their therapeutic or diagnostic use. We also delineate new research avenues to move forward our knowledge on EPC biology.Circulation Research 02/2012; 110(4):624-37. DOI:10.1161/CIRCRESAHA.111.243386 · 11.09 Impact Factor