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

Zhaoyuan Liu, Yaqi Gu, Svetoslav Chakarov, Camille Bleriot, Immanuel Kwok, Xin Chen, Amanda Shin, Weijie Huang, Regine J. Dress, Charles Antoine Dutertre, Andreas Schlitzer, Jinmiao Chen, Lai Guan Ng, Honglin Wang, Zhiduo Liu, Bing Su, Florent Ginhoux

Research output: Contribution to journalArticlepeer-review

357 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1509-1525.e19
JournalCell
Volume178
Issue number6
DOIs
Publication statusPublished - 5 Sept 2019
Externally publishedYes

Keywords

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

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