Plasmacytoid dendritic cells develop from Ly6D+ lymphoid progenitors distinct from the myeloid lineage

Nat Immunol. 2019 Jul;20(7):852-864. doi: 10.1038/s41590-019-0420-3. Epub 2019 Jun 18.

Abstract

Dendritic cells (DC) are currently classified as conventional DCs (cDCs) and plasmacytoid DCs (pDCs). Through a combination of single-cell transcriptomic analysis, mass cytometry, in vivo fate mapping and in vitro clonal assays, here we show that, at the single-cell level, the priming of mouse hematopoietic progenitor cells toward the pDC lineage occurs at the common lymphoid progenitor stage, indicative of early divergence of the pDC and cDC lineages. We found the transcriptional signature of a pDC precursor stage, defined here, in the IL-7Rα+ common lymphoid progenitor population and identified Ly6D, IL-7Rα, CD81 and CD2 as key markers of pDC differentiation, which distinguish pDC precursors from cDC precursors. In conclusion, pDCs developed in the bone marrow from a Ly6DhiCD2hi lymphoid progenitor cell and differentiated independently of the myeloid cDC lineage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Ly / metabolism*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Biomarkers
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Dendritic Cells / cytology*
  • Dendritic Cells / metabolism*
  • Flow Cytometry
  • GPI-Linked Proteins / metabolism
  • Gene Expression
  • Gene Expression Profiling
  • Lymphoid Progenitor Cells / cytology*
  • Lymphoid Progenitor Cells / metabolism*
  • Mice
  • Myeloid Progenitor Cells / cytology*
  • Myeloid Progenitor Cells / metabolism*
  • Transcriptome

Substances

  • Antigens, Ly
  • Biomarkers
  • GPI-Linked Proteins
  • Ly6d protein, mouse