The bone marrow adjusts blood cell production to meet physiological demands in response to insults. The spatial organization of normal and stress responses are unknown owing to the lack of methods to visualize most steps of blood production. Here we develop strategies to image multipotent haematopoiesis, erythropoiesis and lymphopoiesis in mice. We combine these with imaging of myelopoiesis¹ to define the anatomy of normal and stress haematopoiesis. In the steady state, across the skeleton, single stem cells and multipotent progenitors distribute through the marrow enriched near megakaryocytes. Lineage-committed progenitors are recruited to blood vessels, where they contribute to lineage-specific microanatomical structures composed of progenitors and immature cells, which function as the production sites for each major blood lineage. This overall anatomy is resilient to insults, as it was maintained after haemorrhage, systemic bacterial infection and granulocyte colony-stimulating factor (G-CSF) treatment, and during ageing. Production sites enable haematopoietic plasticity as they differentially and selectively modulate their numbers and output in response to insults. We found that stress responses are variable across the skeleton: the tibia and the sternum respond in opposite ways to G-CSF, and the skull does not increase erythropoiesis after haemorrhage. Our studies enable in situ analyses of haematopoiesis, define the anatomy of normal and stress responses, identify discrete microanatomical production sites that confer plasticity to haematopoiesis, and uncover unprecedented heterogeneity of stress responses across the skeleton.

骨髓会调整血细胞的产生，以满足响应损伤的生理需求。由于缺乏可视化大多数血液生成步骤的方法，正常和应激反应的空间组织尚不清楚。在这里，我们开发了对小鼠多能造血、红细胞生成和淋巴细胞生成进行成像的策略。我们将这些与骨髓生成成像¹结合起来，定义正常和应激造血的解剖结构。在稳定状态下，在整个骨骼中，单个干细胞和多能祖细胞分布在巨核细胞附近富集的骨髓中。谱系定向祖细胞被招募到血管中，在那里它们有助于形成由祖细胞和未成熟细胞组成的谱系特异性显微解剖结构，这些结构充当每个主要血液谱系的生产位点。这种整体解剖结构对损伤具有弹性，因为它在出血、全身细菌感染和粒细胞集落刺激因子（G-CSF）治疗后以及衰老过程中得以维持。生产场所能够实现造血可塑性，因为它们有差别地、选择性地调节其数量和输出以应对损伤。我们发现整个骨骼的应激反应是可变的：胫骨和胸骨对 G-CSF 的反应方式相反，并且颅骨在出血后不会增加红细胞生成。我们的研究能够对造血作用进行原位分析，定义正常和应激反应的解剖结构，识别赋予造血作用可塑性的离散微解剖生产位点，并揭示整个骨骼应激反应前所未有的异质性。