English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

Vascular endothelial growth factor (VEGF) and the vascular endothelial growth factor receptors (VEGFRs) regulate the development of hemogenic mesoderm. Oxygen concentration‐mediated activation of hypoxia‐inducible factor targets such as VEGF may serve as the molecular link between the microenvironment and mesoderm‐derived blood and endothelial cell specification. We used controlled‐oxygen microenvironments to manipulate the generation of hemogenic mesoderm and its derivatives from embryonic stem cells. Our studies revealed a novel role for soluble VEGFR1 (sFlt‐1) in modulating hemogenic mesoderm fate between hematopoietic and endothelial cells. Parallel measurements of VEGF and VEGFRs demonstrated that sFlt‐1 regulates VEGFR2 (Flk‐1) activation in both a developmental‐stage‐dependent and oxygen‐dependent manner. Early transient Flk‐1 signaling occurred in hypoxia because of low levels of sFlt‐1 and high levels of VEGF, yielding VEGF‐dependent generation of hemogenic mesoderm. Sustained (or delayed) Flk‐1 activation preferentially yielded hemogenic mesoderm‐derived endothelial cells. In contrast, delayed (sFlt‐1‐mediated) inhibition of Flk‐1 signaling resulted in hemogenic mesoderm‐derived blood progenitor cells. Ex vivo analyses of primary mouse embryo‐derived cells and analysis of transgenic mice secreting a Flt‐1‐Fc fusion protein (Fc, the region of an antibody which is constant and binds to receptors) support a hypothesis whereby microenvironmentally regulated blood and endothelial tissue specification is enabled by the temporally variant control of the levels of Flk‐1 activation.  Disclosure of potential conflicts of interest is found at the end of this article.

Soluble Flt‐1 Regulates Flk‐1 Activation to Control Hematopoietic and Endothelial Development in an Oxygen‐Responsive Manner