Despite the biomedical importance of haematopoietic stem cells and haematopoietic progenitor cells, their in vitro stabilization in a developmental context has not been achieved due to limited knowledge of signals and markers specifying the multiple haematopoietic waves as well as ethically restricted access to the human embryo. Thus, an in vitro approach resembling aspects of haematopoietic development in the context of neighbouring tissues is of interest. Our established human pluripotent stem cell-derived heart-forming organoids (HFOs) recapitulate aspects of heart, vasculature and foregut co-development. Modulating HFO differentiation, we here report the generation of blood-generating HFOs. While maintaining a functional ventricular-like heart anlagen, blood-generating HFOs comprise a mesenchyme-embedded haemogenic endothelial layer encompassing multiple haematopoietic derivatives and haematopoietic progenitor cells with erythro-myeloid and lymphoid potential, reflecting aspects of primitive and definitive haematopoiesis. The model enables the morphologically structured co-development of cardiac, endothelial and multipotent haematopoietic tissues equivalent to the intra-embryonic haematopoietic region in vivo, promoting research on haematopoiesis in vitro.

尽管造血干细胞和造血祖细胞具有生物医学重要性，但由于对指定多个造血波的信号和标志物的了解有限，以及对人类胚胎的伦理限制，它们在发育环境中的体外稳定性尚未实现。因此，一种类似于邻近组织背景下造血发育方面的体外方法是有趣的。我们建立的人类多能干细胞衍生的心脏形成类器官 （HFO） 概括了心脏、脉管系统和前肠共同发育的各个方面。调节 HFO 分化，我们在这里报告了产生血液的 HFO 的产生。在维持功能性心室样心脏抗原的同时，造血 HFO 包括一个间充质嵌入的造血内皮层，该内皮层包含多种造血衍生物和具有红髓和淋巴潜力的造血祖细胞，反映了原始和确定性造血的各个方面。该模型能够实现相当于体内胚胎内造血区域的心脏、内皮和多能造血组织的形态结构共同发育，促进体外造血研究。