Induced pluripotent stem cells (iPSCs) offer a promising platform to model early embryonic developmental processes, to create disease models that can be evaluated by drug screens as well as proof-of-concept experiments for regenerative medicine. However, generation of iPSC-derived hemato-endothelial and hematopoietic progenitor cells for these applications is challenging due to variable and limited cell numbers, which necessitates enormous up-scaling or development of demanding protocols. Here, we unravel the function of key transcriptional regulators SCL, LMO2, GATA2, and ETV2 (SLGE) on early hemato-endothelial specification and establish a fully inducible and stepwise hemato-endothelial forward programming system based on SLGE-regulated overexpression. Regulated induction of SLGE in stable SLGE-iPSC lines drives very efficient generation of large numbers of hemato-endothelial progenitor cells (CD144⁺/CD73^–), which produce hematopoietic progenitor cells (CD45⁺/CD34⁺/CD38^–/CD45RA⁻/CD90⁺/CD49f⁺) through a gradual process of endothelial-to-hematopoietic transition (EHT).

诱导多能干细胞（iPSC）提供了一个有前途的平台，可以为早期胚胎发育过程建模，创建可以通过药物筛选以及再生医学的概念验证实验进行评估的疾病模型。然而，由于可变和有限的细胞数量，用于这些应用的iPSC衍生的造血内皮细胞和造血祖细胞的产生是具有挑战性的，这需要大规模扩大规模或发展有要求的方案。在这里，我们将揭示关键转录调节因子SCL，LMO2，GATA2和ETV2的功能（SLGE）的早期血细胞内皮规范，并建立了基于SLGE调控的过表达的完全可诱导的逐步血细胞内皮正向编程系统。在稳定的SLGE-iPSC系中对SLGE的诱导诱导可非常高效地生成大量的造血内皮祖细胞（CD144 ⁺ / CD73 ^–），从而产生造血祖细胞（CD45 ⁺ / CD34 ⁺ / CD38 ^– / CD45RA ⁻ / CD90 ⁺ / CD49f ⁺）逐步通过内皮细胞向造血细胞的转化（EHT）。