Abstract
Extra-embryonic mesoderm (ExM), the earliest cells that traverse the primitive streak (PS), give rise to the endothelium as well as hematopoietic progenitors in the developing yolk-sac (YS). How a specific subset of ExM becomes committed to a hematopoietic fate remains unclear. Here we demonstrate using an embryonic stem cell (ESC) model that transient expression of the T-box transcription factor Eomesodermin (Eomes) governs hemogenic competency of ExM. Eomes regulates the accessibility of enhancers that SCL normally utilizes to specify primitive erythrocytes and is essential for the normal development of Runx1+ hemogenic endothelium. Single-cell-RNA-seq suggests that Eomes loss-of-function profoundly blocks formation of blood progenitors but not specification of Flk-1+ hematoendothelial progenitors. Our findings place Eomes at the top of the transcriptional hierarchy regulating early blood formation and suggest that hemogenic competence is endowed earlier during embryonic development than previously appreciated.
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