The study investigates the spatial organization and plasticity of hematopoiesis in mice, focusing on the bone marrow's ability to adjust blood cell production in response to physiological demands and stress. Key findings include: 1. **Spatial Organization of Hematopoiesis**: - **Stem Cells and Multipotent Progenitors (MPPs)**: Single stem cells and MPPs are distributed throughout the bone marrow, enriched near megakaryocytes. - **Lineage-Committed Progenitors**: These are recruited to blood vessels and form lineage-specific microanatomical structures, which serve as production sites for mature blood cells. - **Resilience**: The overall anatomy is resilient to insults such as hemorrhage, systemic bacterial infection, and G-CSF treatment, as well as aging. 2. **Hematopoietic Plasticity**: - **Production Sites**: These sites enable hematopoietic plasticity by differentially modulating their numbers and output in response to stress. - **Insult-Specific Adaptation**: Stress responses vary across different bones, with some bones showing opposite responses to G-CSF, and the skull not increasing erythropoiesis after hemorrhage. 3. **Variable Responses Across the Skeleton**: - **G-CSF Treatment**: While it increases granulopoiesis in long bones, it reduces neutrophil production in the sternum. - **Phlebotomy**: Causes an expansion in erythroid production sites in multiple bones but reduces neutrophil production in the sternum. 4. **Discussion**: - The study provides tools and knowledge to study stepwise blood production in situ, defines the anatomy of normal and stress responses, identifies unique production sites, and reveals heterogeneity in stress responses across the skeleton. 5. **Methods**: - The study uses advanced imaging techniques and flow cytometry to visualize and analyze hematopoiesis in various bones and under different stress conditions. Overall, the research highlights the complex and resilient nature of hematopoiesis, emphasizing the importance of production sites in maintaining and adapting to physiological and pathological demands.The study investigates the spatial organization and plasticity of hematopoiesis in mice, focusing on the bone marrow's ability to adjust blood cell production in response to physiological demands and stress. Key findings include: 1. **Spatial Organization of Hematopoiesis**: - **Stem Cells and Multipotent Progenitors (MPPs)**: Single stem cells and MPPs are distributed throughout the bone marrow, enriched near megakaryocytes. - **Lineage-Committed Progenitors**: These are recruited to blood vessels and form lineage-specific microanatomical structures, which serve as production sites for mature blood cells. - **Resilience**: The overall anatomy is resilient to insults such as hemorrhage, systemic bacterial infection, and G-CSF treatment, as well as aging. 2. **Hematopoietic Plasticity**: - **Production Sites**: These sites enable hematopoietic plasticity by differentially modulating their numbers and output in response to stress. - **Insult-Specific Adaptation**: Stress responses vary across different bones, with some bones showing opposite responses to G-CSF, and the skull not increasing erythropoiesis after hemorrhage. 3. **Variable Responses Across the Skeleton**: - **G-CSF Treatment**: While it increases granulopoiesis in long bones, it reduces neutrophil production in the sternum. - **Phlebotomy**: Causes an expansion in erythroid production sites in multiple bones but reduces neutrophil production in the sternum. 4. **Discussion**: - The study provides tools and knowledge to study stepwise blood production in situ, defines the anatomy of normal and stress responses, identifies unique production sites, and reveals heterogeneity in stress responses across the skeleton. 5. **Methods**: - The study uses advanced imaging techniques and flow cytometry to visualize and analyze hematopoiesis in various bones and under different stress conditions. Overall, the research highlights the complex and resilient nature of hematopoiesis, emphasizing the importance of production sites in maintaining and adapting to physiological and pathological demands.