1. Resilient anatomy and local plasticity of naive and stress haematopoiesis.
- Author
-
Wu Q, Zhang J, Kumar S, Shen S, Kincaid M, Johnson CB, Zhang YS, Turcotte R, Alt C, Ito K, Homan S, Sherman BE, Shao TY, Slaughter A, Weinhaus B, Song B, Filippi MD, Grimes HL, Lin CP, Ito K, Way SS, Kofron JM, and Lucas D
- Subjects
- Animals, Female, Male, Mice, Aging physiology, Bacterial Infections pathology, Bacterial Infections physiopathology, Blood Vessels cytology, Cell Lineage, Erythropoiesis, Granulocyte Colony-Stimulating Factor metabolism, Hemorrhage pathology, Hemorrhage physiopathology, Lymphopoiesis, Megakaryocytes cytology, Multipotent Stem Cells cytology, Multipotent Stem Cells metabolism, Myelopoiesis, Skull blood supply, Skull pathology, Skull physiopathology, Sternum blood supply, Sternum cytology, Sternum metabolism, Tibia blood supply, Tibia cytology, Tibia metabolism, Hematopoiesis physiology, Hematopoietic Stem Cells cytology, Hematopoietic Stem Cells metabolism, Stress, Physiological physiology
- 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 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., (© 2024. The Author(s).)- Published
- 2024
- Full Text
- View/download PDF