Freire Ana G, Butler Jason M
Center for Discovery and Innovation, Hackensack University Medical Center, Nutley, USA.
Molecular Oncology Program, Georgetown University, Washington D.C., USA.
F1000Res. 2020 Jan 23;9. doi: 10.12688/f1000research.21245.1. eCollection 2020.
The generation of hematopoietic stem cells (HSCs) from pluripotent stem cell (PSC) sources is a long-standing goal that will require a comprehensive understanding of the molecular and cellular factors that determine HSC fate during embryogenesis. A precise interplay between niche components, such as the vascular, mesenchymal, primitive myeloid cells, and the nervous system provides the unique signaling milieu for the emergence of functional HSCs in the aorta-gonad-mesonephros (AGM) region. Over the last several years, the interrogation of these aspects in the embryo model and in the PSC differentiation system has provided valuable knowledge that will continue educating the design of more efficient protocols to enable the differentiation of PSCs into , functionally transplantable HSCs. Herein, we provide a synopsis of early hematopoietic development, with particular focus on the recent discoveries and remaining questions concerning AGM hematopoiesis. Moreover, we acknowledge the recent advances towards the generation of HSCs and discuss possible approaches to achieve this goal in light of the current knowledge.
从多能干细胞（PSC）来源生成造血干细胞（HSC）是一个长期目标，这需要全面了解在胚胎发育过程中决定HSC命运的分子和细胞因素。龛位成分（如血管、间充质、原始髓样细胞和神经系统）之间精确的相互作用为主动脉-性腺-中肾（AGM）区域功能性HSC的出现提供了独特的信号环境。在过去几年中，对胚胎模型和PSC分化系统中这些方面的研究提供了宝贵的知识，这些知识将继续指导设计更有效的方案，以使PSC分化为功能上可移植的HSC。在此，我们概述早期造血发育，特别关注关于AGM造血的最新发现和遗留问题。此外，我们认可在生成HSC方面的最新进展，并根据当前知识讨论实现这一目标的可能方法。
