Genetic Tracing via DNGR-1 Expression History Defines Dendritic Cells as a Hematopoietic Lineage

Abstract

Mononuclear phagocytes are classified as macrophages or dendritic cells (DCs) based on cell morphology, phenotype, or select functional properties. However, these attributes are not absolute and often overlap, leading to difficulties in cell-type identification. To circumvent this issue, we describe a mouse model to define DCs based on their ontogenetic descendence from a committed precursor. We show that precursors of mouse conventional DCs, but not other leukocytes, are marked by expression of DNGR-1. Genetic tracing of DNGR-1 expression history specifically marks cells traditionally ascribed to the DC lineage, and this restriction is maintained after inflammation. Notably, in some tissues, cells previously thought to be monocytes/macrophages are in fact descendants from DC precursors. These studies provide an in vivo model for fate mapping of DCs, distinguishing them from other leukocyte lineages, and thus help to unravel the functional complexity of the mononuclear phagocyte system.

Selective and efficient generation of functional Batf3-dependent CD103+ dendritic cells from mouse bone marrow

“…34 We speculated that this also holds true for Clec9A, a more specific marker of the CD8a-like cDC lineage, recently shown to be already expressed by DC precursors. 35,36 Interestingly, pre-DCs start to express Clec9A on day 6 and Clec9A expression peaks on day 9, with about 30% of pre-DCs being Clec9A 1 in both FL-DC and iCD103-DC cultures ( Figure 4B-C). Thus, by comparing FL-DC and iCD103-DC cultures, GM-CSF has little effect on Clec9A expression ( Figure 4B) and Clec9A 1 pre-DC numbers ( Figure 4C).…”

Dendritic Cells and Macrophages

“…Renal macrophages expressing very high levels of F4/80 originate mostly from the yolk sac (22) and are more abundant in the medulla (40). Renal mononuclear phagocytes are partially derived from common DC precursors and monocytes (45).…”

CX3CR1 Reduces Kidney Fibrosis by Inhibiting Local Proliferation of Profibrotic Macrophages

“…Tissue macrophages partially originate from embryonic progenitors of the yolk sac or the fetal liver (21,22), and from infiltrating bone marrow-dependent progenitors such as monocytes, whereas DCs can develop from monocytes or pre-DCs (23)(24)(25). The exact contribution of the different precursors to the renal mononuclear cell system is unclear.…”