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

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. [Display omitted] •DNGR-1 marks DC precursors•Tracing DNGR-1 expression history defines conventional DCs•Analysis reveals previously unappreciated DC populations in nonlymphoid tissues•An ontogenetic definition of DCs helps to clarify mononuclear phagocyte function Defining dendritic cells by ontogeny offers a distinct perspective to unraveling the functional complexity of the mononuclear phagocyte system.