Identification of cDC1- And cDC2-committed DC Progenitors Reveals Early Lineage Priming at the Common DC Progenitor Stage in the Bone Marrow

Nat Immunol. 2015 Jul;16(7):718-28. doi: 10.1038/ni.3200. Epub 2015 Jun 8.

Abstract

Mouse conventional dendritic cells (cDCs) can be classified into two functionally distinct lineages: the CD8α(+) (CD103(+)) cDC1 lineage, and the CD11b(+) cDC2 lineage. cDCs arise from a cascade of bone marrow (BM) DC-committed progenitor cells that include the common DC progenitors (CDPs) and pre-DCs, which exit the BM and seed peripheral tissues before differentiating locally into mature cDCs. Where and when commitment to the cDC1 or cDC2 lineage occurs remains poorly understood. Here we found that transcriptional signatures of the cDC1 and cDC2 lineages became evident at the single-cell level from the CDP stage. We also identified Siglec-H and Ly6C as lineage markers that distinguished pre-DC subpopulations committed to the cDC1 lineage (Siglec-H(-)Ly6C(-) pre-DCs) or cDC2 lineage (Siglec-H(-)Ly6C(+) pre-DCs). Our results indicate that commitment to the cDC1 or cDC2 lineage occurs in the BM and not in the periphery.

MeSH terms

  • Animals
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • Antigens, Ly / genetics
  • Antigens, Ly / immunology
  • Antigens, Ly / metabolism
  • Bone Marrow Cells / immunology*
  • Bone Marrow Cells / metabolism
  • CD11b Antigen / immunology
  • CD11b Antigen / metabolism
  • CD8 Antigens / immunology
  • CD8 Antigens / metabolism
  • Cell Lineage / genetics
  • Cell Lineage / immunology*
  • Cells, Cultured
  • Cluster Analysis
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / ultrastructure
  • Flow Cytometry
  • Integrin alpha Chains / immunology
  • Integrin alpha Chains / metabolism
  • Lectins / genetics
  • Lectins / immunology
  • Lectins / metabolism
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Electron, Scanning
  • Oligonucleotide Array Sequence Analysis
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology
  • Receptors, Cell Surface / metabolism
  • Single-Cell Analysis / methods
  • Stem Cells / immunology*
  • Stem Cells / metabolism
  • Transcriptome / genetics
  • Transcriptome / immunology

Substances

  • Antigens, CD
  • Antigens, Ly
  • CD11b Antigen
  • CD8 Antigens
  • CD8alpha antigen
  • Integrin alpha Chains
  • Lectins
  • Ly-6C antigen, mouse
  • Receptors, Cell Surface
  • Siglech protein, mouse
  • alpha E integrins

Associated data

  • GEO/GSE60783