Ezh2 is essential for the generation of functional yolk sac derived erythro-myeloid progenitors [ATAC-seq]

Yolk sac (YS) hematopoiesis is critical for the survival of the embryo and a major source of tissue-resident macrophages that persist into adulthood. Here we report that the epigenetic regulator Ezh2 is essential for YS hematopoiesis but dispensable for subsequent aorta–gonad–mesonephros (AGM) blood development. Loss of Ezh2 activity in hemogenic endothelium (HE) leads to the generation of phenotypically intact but functionally deficient erythro-myeloid progenitors (EMP). Ezh2 activity is critical at the onset of the endothelial-to-hematopoietic transition generating EMPs but rapidly dispensable after that. We identified a lack of downregulation of Wnt signaling as the primary reason in the generation of non-functional EMPs. Together, our findings demonstrate a critical and specific role of Ezh2 in modulating Wnt signaling during the generation of EMPs from YS HE. ATAC-seq profile of E10.5 yolk sac erythro-myeloid progenitors