The article "Origin and Functions of Tissue Macrophages" by Epelman, Lavine, and Randolph reviews the recent advancements in understanding the origin and functions of tissue macrophages. It highlights that most adult tissue macrophages originate during embryonic development rather than from circulating monocytes. The authors discuss the complex interplay between embryonically derived and adult-derived macrophages in different tissues and explore how their functions are regulated by the tissue niche and ontological origin. Key points include: 1. **Origin of Tissue Macrophages**: Macrophages are first observed during early embryonic development in the yolk sac and later in the fetal liver. They are derived from both yolk-sac-derived and definitive hematopoietic stem cell (HSC)-derived progenitors. 2. **Ontological Origins**: Tissue macrophages can be categorized into embryonically derived and adult-derived populations, each with distinct functions. The coexistence of these populations and their specialized roles in different organs are discussed. 3. **Tissue Niche and Ontological Origin**: The tissue niche plays a crucial role in regulating macrophage functions, and the relationship between ontological origin and function is explored. 4. **Monocyte-Specific Origins and Functions**: Monocytes, which originate from HSCs, have two main subsets: classical Ly6Chi monocytes and nonclassical Ly6Clo monocytes. These subsets have distinct functions, with classical monocytes patrolling extravascular tissues and nonclassical monocytes patrolling the vasculature. 5. **Developmental Roles of Macrophages**: The article reviews the roles of embryonic macrophages in various developmental processes, such as vascular development, neuronal patterning, and bone formation. 6. **Dynamics and Function in Tissues**: The dynamics of macrophage recruitment and proliferation in response to injury and disease are discussed, highlighting the importance of monocyte recruitment and local proliferation in tissue repair and regeneration. 7. **Neurodegenerative Diseases**: The role of macrophages in neurodegenerative diseases, such as Alzheimer's, is explored, suggesting that monocyte recruitment may play a protective role. 8. **Cardiac Macrophages**: The article examines the distinct subsets of cardiac macrophages and their functions, including their role in scar formation and inflammation. 9. **Depletion and Plasticity**: The process of macrophage depletion and repopulation, both by resident macrophages and recruited monocytes, is discussed, emphasizing the tissue-specific nature of these processes. 10. **Macrophages and Tissue Regeneration**: The involvement of macrophages in tissue regeneration is highlighted, with a focus on the liver as a well-characterized example. The article concludes by emphasizing the need for further research to understand the specific functions of different macrophage subsets and the interplay between resident and recruited macrophages in various physiological and pathological contexts.The article "Origin and Functions of Tissue Macrophages" by Epelman, Lavine, and Randolph reviews the recent advancements in understanding the origin and functions of tissue macrophages. It highlights that most adult tissue macrophages originate during embryonic development rather than from circulating monocytes. The authors discuss the complex interplay between embryonically derived and adult-derived macrophages in different tissues and explore how their functions are regulated by the tissue niche and ontological origin. Key points include: 1. **Origin of Tissue Macrophages**: Macrophages are first observed during early embryonic development in the yolk sac and later in the fetal liver. They are derived from both yolk-sac-derived and definitive hematopoietic stem cell (HSC)-derived progenitors. 2. **Ontological Origins**: Tissue macrophages can be categorized into embryonically derived and adult-derived populations, each with distinct functions. The coexistence of these populations and their specialized roles in different organs are discussed. 3. **Tissue Niche and Ontological Origin**: The tissue niche plays a crucial role in regulating macrophage functions, and the relationship between ontological origin and function is explored. 4. **Monocyte-Specific Origins and Functions**: Monocytes, which originate from HSCs, have two main subsets: classical Ly6Chi monocytes and nonclassical Ly6Clo monocytes. These subsets have distinct functions, with classical monocytes patrolling extravascular tissues and nonclassical monocytes patrolling the vasculature. 5. **Developmental Roles of Macrophages**: The article reviews the roles of embryonic macrophages in various developmental processes, such as vascular development, neuronal patterning, and bone formation. 6. **Dynamics and Function in Tissues**: The dynamics of macrophage recruitment and proliferation in response to injury and disease are discussed, highlighting the importance of monocyte recruitment and local proliferation in tissue repair and regeneration. 7. **Neurodegenerative Diseases**: The role of macrophages in neurodegenerative diseases, such as Alzheimer's, is explored, suggesting that monocyte recruitment may play a protective role. 8. **Cardiac Macrophages**: The article examines the distinct subsets of cardiac macrophages and their functions, including their role in scar formation and inflammation. 9. **Depletion and Plasticity**: The process of macrophage depletion and repopulation, both by resident macrophages and recruited monocytes, is discussed, emphasizing the tissue-specific nature of these processes. 10. **Macrophages and Tissue Regeneration**: The involvement of macrophages in tissue regeneration is highlighted, with a focus on the liver as a well-characterized example. The article concludes by emphasizing the need for further research to understand the specific functions of different macrophage subsets and the interplay between resident and recruited macrophages in various physiological and pathological contexts.