Identification of clonogenic common Flt3+M-CSFR+ plasmacytoid and conventional dendritic cell progenitors in mouse bone marrow.

Lymphoid tissue plasmacytoid and conventional dendritic cells (DCs) are continuously regenerated from hematopoietic stem cells. The cytokine dependence and biology of plasmacytoid and conventional DCs suggest that regeneration might proceed through common DC-restricted developmental intermediates. By selecting for cytokine receptor expression relevant to DC development, we identify here highly cycling Lin(-)c-Kit(int)Flt3(+)M-CSFR(+) cells with a distinct gene-expression profile in mouse bone marrow that, on a clonal level in vitro and as a population both in vitro and in vivo, efficiently generated plasmacytoid and conventional DCs but no other lineages, which increased in number after in vivo injection of the cytokine Flt3 ligand. These clonogenic common DC progenitors thus define a cytokine-regulated DC developmental pathway that ensures the supply of various DC populations.