Resilient anatomy and local plasticity of naive and stress haematopoiesis

• 成果类型: Article
• 署名作者: Wu, Qingqing; Zhang, Jizhou; Kumar, Sumit; Shen, Siyu; Kincaid, Morgan; Johnson, Courtney B.; Zhang, Yanan Sophia; Turcotte, Raphael; Alt, Clemens; Ito, Kyoko; Homan, Shelli; Sherman, Bryan E.; Shao, Tzu-Yu; Slaughter, Anastasiya; Weinhaus, Benjamin; Song, Baobao; Filippi, Marie Dominique; Grimes, H. Leighton; Lin, Charles P.; Ito, Keisuke; Way, Sing Sing; Kofron, J. Matthew; Lucas, Daniel
• 署名单位: Cincinnati Children's Hospital Medical Center; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; University System of Ohio; University of Cincinnati; Cincinnati Children's Hospital Medical Center; University System of Ohio; University of Cincinnati; Cincinnati Children's Hospital Medical Center; University System of Ohio; University of Cincinnati; Cincinnati Children's Hospital Medical Center; University System of Ohio; University of Cincinnati; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; Harvard University; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Cincinnati Children's Hospital Medical Center; Chinese Academy of Sciences; University of Science & Technology of China, CAS
• 刊物名称: Nature
• ISSN/ISSBN: 0028-6745
• DOI: 10.1038/s41586-024-07186-6
• 发表日期: 2024-03-28
• 页码: 839-+
• 关键词: stem-cells; myeloid progenitor; niches; identification; subset; esam

摘要

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 myelopoiesis(1) 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.