GATA2 is essential for the endothelial-to-hematopoietic transition (EHT) and generation of hematopoietic stem cells (HSCs). It is poorly understood how GATA2 controls the development of human pluripotent stem cell (hPSC)-derived HS-like cells. Here, using human embryonic stem cells (hESCs) in which GATA2 overexpression was induced by doxycycline (Dox), we elucidated the dual functions of GATA2 in definitive hematopoiesis before and after the emergence of CD34⁺CD45⁺CD90⁺CD38^– HS-like cells. Specifically, GATA2 promoted expansion of hemogenic precursors via the EHT and then helped to maintain HS-like cells in a quiescent state by regulating cell cycle. RNA sequencing showed that hPSC-derived HS-like cells were very similar to human fetal liver-derived HSCs. Our findings will help to elucidate the mechanism that controls the early stages of human definitive hematopoiesis and may help to develop a strategy to generate hPSC-derived HSCs.

GATA2对于内皮细胞向造血细胞的过渡（EHT）和造血干细胞（HSC）的生成至关重要。人们对GATA2如何控制人类多能干细胞（hPSC）衍生的HS样细胞的发育了解甚少。在这里，我们利用强力霉素（Dox）诱导GATA2过表达的人类胚胎干细胞（hESCs），阐明了CD34 ⁺ CD45 ⁺ CD90 ⁺ CD90 ⁺ CD38出现前后，GATA2在确定性造血中的双重功能^–HS样细胞。具体而言，GATA2通过EHT促进了造血前体的扩增，然后通过调节细胞周期帮助将HS样细胞维持在静止状态。RNA测序表明，hPSC衍生的HS样细胞与人胎儿肝脏衍生的HSCs非常相似。我们的发现将有助于阐明控制人类定型造血早期阶段的机制，并可能有助于制定产生hPSC来源的HSC的策略。