造血心脏形成类器官概括了人类造血系统和胚胎心脏的共同发育。
Blood-generating heart-forming organoids recapitulate co-development of the human haematopoietic system and the embryonic heart.
发表日期:2024 Oct 08
作者:
Miriana Dardano, Felix Kleemiß, Maike Kosanke, Dorina Lang, Liam Wilson, Annika Franke, Jana Teske, Akshatha Shivaraj, Jeanne de la Roche, Martin Fischer, Lucas Lange, Axel Schambach, Lika Drakhlis, Robert Zweigerdt
来源:
NATURE CELL BIOLOGY
摘要:
尽管造血干细胞和造血祖细胞具有生物医学重要性,但由于对指定多种造血波的信号和标记物的了解有限以及进入人类胚胎的伦理限制,它们在发育背景下的体外稳定性尚未实现。因此,在邻近组织的背景下类似于造血发育方面的体外方法是令人感兴趣的。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。通过调节 HFO 分化,我们在此报告了造血 HFO 的生成。在维持功能性心室样心脏原基的同时,造血 HFO 包含嵌入间充质的造血内皮层,其中包含多种造血衍生物和具有红髓和淋巴潜能的造血祖细胞,反映了原始和最终造血的各个方面。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。© 2024。作者。
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.© 2024. The Author(s).