Blood production depends on rare haematopoietic stem cells (HSCs) and haematopoietic stem and progenitor cells (HSPCs) that ultimately take up residence in the bone marrow during development. HSPCs and HSCs are subject to extrinsic regulation by the bone marrow microenvironment, or niche. Studying the interactions between HSCs and their niche is critical for improving ex vivo culturing conditions and genetic manipulation of HSCs, which is pivotal for improving autologous HSC therapies and transplantations. Additionally, understanding how the complex molecular network in the bone marrow is altered during ageing is paramount for developing novel therapeutics for ageing-related haematopoietic disorders. HSCs are unique amongst stem and progenitor cell pools in that they engage with multiple physically distinct niches during their ontogeny. HSCs are specified from haemogenic endothelium in the aorta, migrate to the fetal liver and, ultimately, colonize their final niche in the bone marrow. Recent studies employing single-cell transcriptomics and microscopy have identified novel cellular interactions that govern HSC specification and engagement with their niches throughout ontogeny. New lineage-tracing models and microscopy tools have raised questions about the numbers of HSCs specified, as well as the functional consequences of HSCs interacting with each developmental niche. Advances have also been made in understanding how these niches are modified and perturbed during ageing, and the role of these altered interactions in haematopoietic diseases. In this Review, we discuss these new findings and highlight the questions that remain to be explored.

血液的产生取决于稀有的造血干细胞 (HSC) 以及造血干细胞和祖细胞 (HSPC)，它们最终在发育过程中驻留在骨髓中。 HSPC 和 HSC 受到骨髓微环境或生态位的外在调节。研究 HSC 与其生态位之间的相互作用对于改善 HSC 的离体培养条件和基因操作至关重要，这对于改善自体 HSC 治疗和移植至关重要。此外，了解衰老过程中骨髓中复杂的分子网络如何改变对于开发针对衰老相关造血疾病的新疗法至关重要。 HSC 在干细胞和祖细胞库中是独一无二的，因为它们在个体发育过程中参与多个物理上不同的生态位。造血干细胞从主动脉的造血内皮细胞中分化出来，迁移到胎儿肝脏，并最终在骨髓中定居。最近采用单细胞转录组学和显微镜的研究已经发现了新的细胞相互作用，这些相互作用控制着 HSC 的规范以及在整个个体发育过程中与其生态位的参与。新的谱系追踪模型和显微镜工具对指定的 HSC 数量以及 HSC 与每个发育生态位相互作用的功能后果提出了疑问。在了解这些生态位在衰老过程中如何被改变和扰动以及这些改变的相互作用在造血疾病中的作用方面也取得了进展。在这篇综述中，我们讨论了这些新发现并强调了仍有待探索的问题。