Resilient anatomy and local plasticity of naive and stress haematopoiesis

Wu, Qingqing and Zhang, Jizhou and Kumar, Sumit and Shen, Siyu and Kincaid, Morgan and Johnson, Courtney B. and Zhang, Yanan Sophia and Turcotte, Raphaël and Alt, Clemens and Ito, Kyoko and Homan, Shelli and Sherman, Bryan E. and Shao, Tzu-Yu and Slaughter, Anastasiya and Weinhaus, Benjamin and Song, Baobao and Filippi, Marie Dominique and Grimes, H. Leighton and Lin, Charles P. and Ito, Keisuke and Way, Sing Sing and Kofron, J. Matthew and Lucas, Daniel (2024) Resilient anatomy and local plasticity of naive and stress haematopoiesis. Nature. ISSN 0028-0836

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Abstract

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.

Item Type: Article
Subjects: Open Research Librarians > Multidisciplinary
Depositing User: Unnamed user with email support@open.researchlibrarians.com
Date Deposited: 21 Mar 2024 06:26
Last Modified: 21 Mar 2024 06:26
URI: http://stm.e4journal.com/id/eprint/2548

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