Identification of Clonogenic Common Flt3+M-CSFR+ Plasmacytoid and Conventional Dendritic Cell Progenitors in Mouse Bone Marrow

Nat Immunol. 2007 Nov;8(11):1207-16. doi: 10.1038/ni1518. Epub 2007 Oct 7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / immunology*
  • Bone Marrow Cells / metabolism
  • Cell Differentiation / immunology
  • Cell Lineage / immunology
  • Clone Cells
  • Dendritic Cells / cytology*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Flow Cytometry
  • Gene Expression
  • Gene Expression Profiling
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / metabolism
  • Lymphocyte Culture Test, Mixed
  • Mice
  • Mice, Inbred C57BL
  • Receptor, Macrophage Colony-Stimulating Factor / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • fms-Like Tyrosine Kinase 3 / metabolism*

Substances

  • Flt3 protein, mouse
  • Receptor, Macrophage Colony-Stimulating Factor
  • fms-Like Tyrosine Kinase 3