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Published on: July 17, 2017
A role for macrophages in hematopoiesis in the embryonic head
Zhuan Li1,2, Samanta A Mariani1, Carmen Rodriguez-Seoane1
1Centre for Inflammation Research, The University of Edinburgh, Edinburgh, United Kingdom.
Abstract:
Along with the aorta-gonad-mesonephros region, the head is a site of hematopoietic stem and progenitor cell (HS/PC) development in the mouse embryo. Macrophages are present in both these embryonic hemogenic sites, and recent studies indicate a functional interaction of macrophages with hematopoietic cells as they are generated in the aorta. Whereas brain macrophages or "microglia" are known to affect neuronal patterning and vascular circuitry in the embryonic brain, it is unknown whether macrophages play a role in head hematopoiesis. Here, we characterize head macrophages and examine whether they affect the HS/PC output of the hindbrain-branchial arch (HBA) region of the mouse embryo. We show that HBA macrophages are CD45+F4/80+CD11b+Gr1- and express the macrophage-specific Csf1r-GFP reporter. In the HBA of chemokine receptor-deficient (Cx3cr1-/-) embryos, a reduction in erythropoiesis is concomitant with a decrease in HBA macrophage percentages. In cocultures, we show that head macrophages boost hematopoietic progenitor cell numbers from HBA endothelial cells > twofold, and that the proinflammatory factor tumor necrosis factor-α is produced by head macrophages and influences HBA hematopoiesis in vitro. Taken together, head macrophages play a positive role in HBA erythropoiesis and HS/PC expansion and/or maturation, acting as microenvironmental cellular regulators in hematopoietic development.
Insights
Head macrophages positively regulate embryonic blood cell development in the hindbrain-branchial arch (HBA) region. These macrophages boost hematopoietic stem and progenitor cell (HS/PC) numbers and influence erythropoiesis.
Area of Science:
- Developmental biology
- Hematopoiesis
- Immunology
Background:
- The head is a key site for embryonic blood stem and progenitor cell (HS/PC) development.
- Macrophages are present in embryonic hemogenic sites and interact with developing hematopoietic cells.
- The role of head macrophages in embryonic hematopoiesis remains unclear.
Purpose of the Study:
- To characterize head macrophages in mouse embryos.
- To investigate the impact of head macrophages on HS/PC output from the hindbrain-branchial arch (HBA) region.
- To determine if head macrophages influence embryonic erythropoiesis.
Main Methods:
- Characterization of HBA macrophages using flow cytometry and reporter gene expression (Csf1r-GFP).
- Analysis of HBA hematopoiesis in chemokine receptor-deficient (Cx3cr1-/-) embryos.
- Coculture experiments with head macrophages and HBA endothelial cells.
- Assessment of cytokine production (tumor necrosis factor-α) by head macrophages.
Main Results:
- HBA macrophages express specific macrophage markers (CD45+F4/80+CD11b+Gr1-) and Csf1r-GFP.
- Absence of Cx3cr1 leads to reduced erythropoiesis and fewer HBA macrophages.
- Head macrophages significantly increase hematopoietic progenitor cell numbers from HBA endothelial cells in vitro.
- Head macrophages produce tumor necrosis factor-α, which influences HBA hematopoiesis.
Conclusions:
- Head macrophages play a crucial positive role in HBA erythropoiesis and HS/PC expansion/maturation.
- Head macrophages act as essential microenvironmental regulators of embryonic hematopoietic development.
- These findings highlight the intricate interplay between macrophages and hematopoiesis in the developing head.
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