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Developmental derivation of embryonic and adult macrophages
1Children's Hospital, Department of Medicine, Boston, Massachusetts 02115, USA.
Abstract:
The macrophage cell lineage continually arises from hematopoietic stem cells during embryonic, fetal, and adult life. Previous theories proposed that macrophages are the recent progeny of bone marrow-derived monocytes and that they function primarily in phagocytosis. More recently, however, observations have shown that the ontogeny of macrophages in early mouse and human embryos is different from that occurring during adult development, and that the embryonic macrophages do not follow the monocyte pathway. Fetal macrophages are thought to differentiate from yolk sac-derived primitive macrophages before the development of adult monocytes. Further support for a separate lineage of fetal macrophages has come from studies of several species, including chicken, zebrafish, Xenopus, Drosophila, and C. elegans. The presence of fetal macrophages in PU.1-null mice indicates their independence from monocyte precursors and their existence as an alternative macrophage lineage.
Insights
Macrophages arise from stem cells throughout life. Recent findings reveal distinct embryonic and fetal macrophage lineages separate from adult monocyte pathways, challenging previous theories.
Area of Science:
- Immunology
- Developmental Biology
- Cell Biology
Background:
- Macrophages are crucial immune cells originating from hematopoietic stem cells.
- Historically, macrophages were believed to develop solely from adult bone marrow-derived monocytes.
- Recent research suggests alternative origins and developmental pathways for macrophages.
Purpose of the Study:
- To investigate the ontogeny of macrophages during embryonic and fetal development.
- To determine if embryonic/fetal macrophages follow the same developmental pathway as adult macrophages.
- To explore the existence of separate macrophage lineages.
Main Methods:
- Comparative analysis of macrophage development in embryonic, fetal, and adult stages.
- Studies across multiple species including mouse, human, chicken, zebrafish, Xenopus, Drosophila, and C. elegans.
- Examination of macrophage development in PU.1-null mice.
Main Results:
- Embryonic and fetal macrophage development differs significantly from adult development.
- Embryonic macrophages do not originate from the monocyte pathway.
- Fetal macrophages appear to develop from yolk sac-derived primitive macrophages prior to adult monocyte emergence.
- Macrophages exist in PU.1-null mice, confirming an alternative lineage independent of monocyte precursors.
Conclusions:
- Macrophages arise from distinct developmental lineages, not solely from adult monocytes.
- A separate lineage of fetal macrophages exists, originating independently of the monocyte pathway.
- These findings necessitate a revised understanding of macrophage ontogeny and immune cell development.