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

胚胎外中胚层（ExM）由最早穿过原条的细胞组成，在发育中的卵黄囊中产生内皮细胞和造血祖细胞。 ExM 的特定子集如何决定造血命运仍不清楚。在这里，我们使用胚胎干细胞模型证明 T 盒转录因子 Eomesodermin (Eomes) 的瞬时表达控制 ExM 的造血能力。 Eomes 调节增强子的可及性，转录因子干细胞白血病 (SCL) 通常利用增强子来指定原始红细胞，并且对于 Runx1 ⁺造血内皮的正常发育至关重要。单细胞 RNA 测序表明，Eomes 功能丧失会严重阻碍血液祖细胞的形成，但不会阻碍 Flk-1 ⁺血液内皮祖细胞的形成。我们的研究结果将 Eomes 置于调节早期血液形成的转录层次结构的顶部，并表明在胚胎发育过程中，造血能力的赋予比以前认为的更早。