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Cell. 2019 Sep 5;178(6):1509-1525.e19. doi: 10.1016/j.cell.2019.08.009.

Fate Mapping via Ms4a3-Expression History Traces Monocyte-Derived Cells.

Author information

1
Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
2
Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore.
3
Myeloid Cell Biology, LIMES-Institute, University of Bonn, 53115 Bonn, Germany.
4
Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: bingsu@sjtu.edu.cn.
5
Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore; Translational Immunology Institute, SingHealth Duke-NUS Academic Medical Centre, Singapore, Singapore. Electronic address: florent_ginhoux@immunol.a-star.edu.sg.

Abstract

Most tissue-resident macrophage (RTM) populations are seeded by waves of embryonic hematopoiesis and are self-maintained independently of a bone marrow contribution during adulthood. A proportion of RTMs, however, is constantly replaced by blood monocytes, and their functions compared to embryonic RTMs remain unclear. The kinetics and extent of the contribution of circulating monocytes to RTM replacement during homeostasis, inflammation, and disease are highly debated. Here, we identified Ms4a3 as a specific gene expressed by granulocyte-monocyte progenitors (GMPs) and subsequently generated Ms4a3TdT reporter, Ms4a3Cre, and Ms4a3CreERT2 fate-mapping models. These models traced efficiently monocytes and granulocytes, but no lymphocytes or tissue dendritic cells. Using these models, we precisely quantified the contribution of monocytes to the RTM pool during homeostasis and inflammation. The unambiguous identification of monocyte-derived cells will permit future studies of their function under any condition.

KEYWORDS:

GMP; MDP; Ms4a3; dendritic cell; fate mapping; granulocyte-monocyte progenitor; inflammation; monocyte; monocyte-dendritic cell progenitor; tissue-resident macrophage

PMID:
31491389
DOI:
10.1016/j.cell.2019.08.009

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