Vascular Tumors and Developmental Malformations by Paula E. North & Tara Sander

Author:Paula E. North & Tara Sander
Language: eng
Format: epub
Publisher: Springer New York, New York, NY

The Case for Hemangioblast

Nearly a century ago, based on observations in chick embryos that both hematopoietic and ECs are closely situated and develop together, a new term called “hemangioblast” was proposed to describe the common precursor cell [14, 15] that gives rise to both lineages. In terms of model systems, zebrafish has contributed immensely to our understanding of hemangioblast because of the identification of the first genetic mutant in vertebrate, “cloche,” which lacks both ECs and blood cells suggesting that the mutation lies in the critical gene (as yet unidentified) that specifies the critical dual potential hemangioblast cell to vascular and blood lineage [16, 17]. More recently, Vogeli and his group constructed single-cell-resolution fate maps that show individual cells in zebrafish late blastula and gastrula can give rise to both hematopoietic and ECs [18]. Substantial characterization of the hemangioblasts has occurred in vitro through the utilization of the embryonic stem cell (ESC)-derived embryoid body (EB) model system . In the mouse and human ESC-derived EB cultures, single blast colony-forming cells (BL-CFCs) generate colonies that contain both hematopoietic and ECs. These cells emerge in the presence of VEGF-A and bone morphogenetic protein-4 (BMP-4) [10, 19, 20]. Further, they express flk-1 and the mesodermal marker brachyury [21]. Based on the ability of genetically engineered ESCs to differentiate into BL-CFCs in vitro, flk-1, Scl, Runx-1, Hhex, Mixl-1, Bmp-4, Smad-1, Gata-2, and Lycat have all been shown to be essential for the generation of BL-CFCs [22–31]. In addition to these genes, Lmo, fli-1, and etsrp have been recently implicated in the specification of hemangioblast from the posterior LPM in zebrafish [32–37]. Importantly, constitutive activation of fli1 is shown to be sufficient to induce expression of key hemangioblast genes such as scl, lmo, gata2, etsrp, and flk-1 [38]. At present, our knowledge of hemangioblast specification from LPM is emerging; however, our knowledge downstream of hemangioblast is better known, as will be discussed in the next section.

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