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Immunity. 2019 Jun 18;50(6):1439-1452.e5. doi: 10.1016/j.immuni.2019.05.003. Epub 2019 Jun 6.

Pro-inflammatory Aorta-Associated Macrophages Are Involved in Embryonic Development of Hematopoietic Stem Cells.

Author information

1
Centre for Inflammation Research, The University of Edinburgh, Edinburgh, UK. Electronic address: s.mariani@ed.ac.uk.
2
Centre for Inflammation Research, The University of Edinburgh, Edinburgh, UK.
3
Medical University of South Carolina, Charleston, SC, USA.
4
MRC Centre for Reproductive Health, The University of Edinburgh, Edinburgh, UK.
5
University of Zurich, Zurich, Switzerland.
6
Centre for Inflammation Research, The University of Edinburgh, Edinburgh, UK. Electronic address: elaine.dzierzak@ed.ac.uk.

Abstract

Hematopoietic stem cells (HSCs) are generated from specialized endothelial cells of the embryonic aorta. Inflammatory factors are implicated in regulating mouse HSC development, but which cells in the aorta-gonad-mesonephros (AGM) microenvironment produce these factors is unknown. In the adult, macrophages play both pro- and anti-inflammatory roles. We sought to examine whether macrophages or other hematopoietic cells found in the embryo prior to HSC generation were involved in the AGM HSC-generative microenvironment. CyTOF analysis of CD45+ AGM cells revealed predominance of two hematopoietic cell types, mannose-receptor positive macrophages and mannose-receptor negative myeloid cells. We show here that macrophage appearance in the AGM was dependent on the chemokine receptor Cx3cr1. These macrophages expressed a pro-inflammatory signature, localized to the aorta, and dynamically interacted with nascent and emerging intra-aortic hematopoietic cells (IAHCs). Importantly, upon macrophage depletion, no adult-repopulating HSCs were detected, thus implicating a role for pro-inflammatory AGM-associated macrophages in regulating the development of HSCs.

KEYWORDS:

AGM; CD206; Csf1r; Cx3cr1; MacGreen; hematopoietic development; hematopoietic stem cell; inflammation; macrophage; mannose receptor

PMID:
31178352
PMCID:
PMC6591003
DOI:
10.1016/j.immuni.2019.05.003
[Indexed for MEDLINE]
Free PMC Article

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