Ezh2 is essential for the generation of functional yolk sac derived erythro-myeloid progenitors [RNA-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. RNA-seq profile of E10.5 yolk sac erythro-myeloid progenitors卵黄囊（Yolk sac, YS）造血作用对胚胎存活至关重要，同时亦是终生存留的组织驻留巨噬细胞的主要来源。本研究证实，表观遗传调控因子Ezh2对卵黄囊造血作用必不可少，但对后续主动脉-性腺-中肾区（aorta-gonad-mesonephros, AGM）的血液发育并非必需。生血内皮细胞（hemogenic endothelium, HE）中Ezh2功能缺失，会导致表型完整但功能缺陷的红系-髓系祖细胞（erythro-myeloid progenitors, EMP）生成。Ezh2的功能在红系-髓系祖细胞生成过程中的内皮-造血转化起始阶段至关重要，但在此之后便迅速不再必需。我们发现，Wnt信号通路的下调缺失是生成功能缺陷红系-髓系祖细胞的主要原因。综上，本研究结果揭示了Ezh2在卵黄囊生血内皮细胞生成红系-髓系祖细胞过程中，通过调控Wnt信号通路发挥的关键且特异性的作用。本数据集包含E10.5卵黄囊红系-髓系祖细胞的RNA测序转录组谱。