Hematopoietic stem cells (HSCs) are the rare cells responsible for the lifelong curative effects of hematopoietic cell (HC) transplantation. The demand for clinical-grade HSCs has increased significantly in recent decades, leading to major difficulties in treating patients. A promising but not yet achieved goal is the generation of HSCs from pluripotent stem cells. Here, we have obtained vector- and stroma-free transplantable HSCs by differentiating human induced pluripotent stem cells (hiPSCs) using an original one-step culture system. After injection into immunocompromised mice, cells derived from hiPSCs settle in the bone marrow and form a robust multilineage hematopoietic population that can be serially transplanted. Single-cell RNA sequencing shows that this repopulating activity is due to a hematopoietic population that is transcriptionally similar to human embryonic aorta-derived HSCs. Overall, our results demonstrate the generation of HSCs from hiPSCs and will help identify key regulators of HSC production during human ontogeny.

造血干细胞（HSC）是造血细胞（HC）移植产生终生疗效的稀有细胞。近几十年来，对临床级造血干细胞的需求显着增加，导致治疗患者面临重大困难。一个有希望但尚未实现的目标是利用多能干细胞生成造血干细胞。在这里，我们使用原始的一步培养系统分化人类诱导多能干细胞（hiPSC），获得了无载体和无基质的可移植 HSC 。注射到免疫功能低下的小鼠体内后，源自 hiPSC 的细胞会定居在骨髓中，并形成强大的多谱系造血群体，可以连续移植。单细胞 RNA 测序表明，这种重新增殖活性是由于造血细胞群在转录上与人类胚胎主动脉衍生的 HSC 相似。总体而言，我们的结果证明了 hiPSC 生成 HSC 的过程，并将有助于确定人类个体发育过程中 HSC 产生的关键调节因子。