Pro-inflammatory aorta-associated macrophages are involved in embryonic development of hematopoietic stem cells

Samanta Antonella Mariani, Zhuan Li, Siobhan Rice, Carsten Krieg, Stamatina Fragkogianni, Mark Robinson, Chris Sebastiaan Vink, Jeffrey William Pollard, Elaine Dzierzak

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)1439-1452.E5
Number of pages19
JournalImmunity
Volume50
Issue number6
Early online date8 Jun 2019
DOIs
Publication statusPublished - 18 Jun 2019

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