The Hemogenic Competence of Endothelial Progenitors Is Restricted by Runx1 Silencing during Embryonic Development.

It is now well-established that hematopoietic stem cells (HSCs) and progenitor cells originate from a specialized subset of endothelium, termed hemogenic endothelium (HE), via an endothelial-to-hematopoietic transition. However, the molecular mechanisms determining which endothelial progenitors possess this hemogenic potential are currently unknown. Here, we investigated the changes in hemogenic potential in endothelial progenitors at the early stages of embryonic development.

ETV2 expression marks blood and endothelium precursors, including hemogenic endothelium, at the onset of blood development.

Background: ETV2 has been identified as an important player in embryonic hematopoiesis. However, the cell populations in which this transcription factor is expressed and operates during blood specification remain to be fully characterized. Here we address these issues using ES cells and a transgenic mouse line expressing green fluorescent protein (GFP) under the control of ETV2 regulatory elements, allowing us to observe the tight association between ETV2 expression and the initiation of hematopoiesis.

The Flk1-Cre-mediated deletion of ETV2 defines its narrow temporal requirement during embryonic hematopoietic development.

During embryonic development, the emergence of hematopoiesis and vasculogenesis is tightly associated, with many transcription factors implicated in both developmental processes. Among those factors, ETV2 acts at the top of the hierarchy and controls the formation of both lineages. However, it is not known at which stage of mesoderm development ETV2 is acting and whether ETV2 activity is further required once mesodermal precursors have been specified to the hematopoietic and endothelial fates.