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Development and heterogeneity of macrophages and their related cells through their differentiation pathways
K Takahashi1, M Naito, M Takeya
1Second Department of Pathology, Kumamoto University Medical School, Japan.
Abstract:
Macrophages are a heterogeneous population differing in their site of location, morphology and function. They develop from hematopoietic stem cells originating in both fetal and bone marrow hematopoiesis. In yolk sac and early hepatic hematopoiesis, primitive/fetal macrophages develop from hematopoietic stem cells, bypassing the stage of monocytic cells (monoblasts, promonocytes and monocytes), possess proliferative capacity and differentiate into resident macrophages in tissues in late ontogeny. Monocytic cells develop in hepatic hematopoiesis after the development of primitive/fetal macrophages, then move into the bone marrow in late ontogeny, forming a monocyte-derived macrophage population in tissues. Like monocytes, the monocyte-derived macrophages have no proliferative potential and are short-lived, whereas the resident macrophages are long-lived in tissue, possess proliferative capacity and can be sustained by self-renewal. In adult life, the bone marrow releases macrophage precursors (immature myeloid cells) and monocytes into peripheral blood, but normally not monoblasts or promonocyts. The myeloid precursor cells migrate into tissues and differentiate into resident macrophages or related cells in situ due to macrophage differentiation or growth factors, such as M-CSF and GM-CSF, produced in situ and/or supplied humorally. Monocytes, however, migrate into tissues in response to inflammatory stimuli and differentiate into exudate macrophages. The distinct differentiation pathways of monocyte/macrophages, resident macrophages, other macrophage subpopulations, and macrophage-related cells are reviewed together with the heterogeneity of macrophage precursor cells.
Insights
Macrophages exhibit diverse origins and functions, developing from fetal or adult hematopoietic stem cells. Understanding these distinct pathways, including resident and monocyte-derived macrophages, is crucial for comprehending their roles in tissue homeostasis and inflammation.
Area of Science:
- Immunology
- Developmental Biology
- Cell Biology
Background:
- Macrophages are critical immune cells with diverse roles, originating from hematopoietic stem cells.
- Their development involves distinct pathways during fetal and adult life, leading to varied subpopulations.
- Heterogeneity in macrophage origin, morphology, and function impacts tissue-specific roles.
Purpose of the Study:
- To review the distinct differentiation pathways of macrophages.
- To elucidate the origins and heterogeneity of macrophage precursor cells.
- To differentiate between resident and monocyte-derived macrophages.
Main Methods:
- Review of existing literature on macrophage development and differentiation.
- Analysis of hematopoietic stem cell origins in fetal and adult hematopoiesis.
- Comparison of differentiation pathways of various macrophage subpopulations.
Main Results:
- Primitive/fetal macrophages arise early, bypassing monocytic stages and possessing proliferative capacity.
- Monocyte-derived macrophages develop later, lack proliferative potential, and are short-lived.
- Adult bone marrow releases macrophage precursors and monocytes, differentiating into resident and exudate macrophages, respectively.
Conclusions:
- Macrophages are highly heterogeneous, with distinct developmental trajectories influencing their function.
- Resident macrophages are long-lived and self-renewing, while monocyte-derived macrophages are transient.
- Understanding these pathways is key to understanding immune responses and tissue repair.