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

Area of Science:

• Immunology
• Hematopoiesis
• Cell Biology

Background:

• Tissue-resident macrophages (RTMs) are primarily established during embryonic development and self-maintain.
• A subset of RTMs is continuously replenished by circulating monocytes, but their contribution and function remain poorly understood.
• The precise extent and kinetics of monocyte-derived RTMs during various physiological and pathological states are debated.

Purpose of the Study:

• To develop a reliable method for tracing monocyte-derived cells within RTM populations.
• To quantify the contribution of circulating monocytes to RTMs during homeostasis and inflammation.
• To establish a foundation for future functional studies of monocyte-derived RTMs.

Main Methods:

• Identification of Ms4a3 as a specific gene marker in granulocyte-monocyte progenitors (GMPs).
• Generation of Ms4a3 reporter (Ms4a3^TdT), Cre (Ms4a3^Cre), and inducible Cre (Ms4a3^CreERT2) mouse models.
• Utilizing fate-mapping strategies to trace monocyte and granulocyte populations, excluding lymphocytes and tissue dendritic cells.

Main Results:

• Ms4a3 expression was confirmed in GMPs, enabling specific lineage tracing.
• The developed Ms4a3 fate-mapping models accurately traced monocytes and granulocytes.
• Precise quantification of monocyte contribution to the RTM pool during homeostasis and inflammation was achieved.

Conclusions:

• Ms4a3 serves as a specific and effective marker for tracing monocyte and granulocyte lineages.
• This study provides a robust tool for the unambiguous identification of monocyte-derived cells in RTM populations.
• The established models will facilitate future investigations into the functional roles of monocyte-derived RTMs in health and disease.