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Restricted dendritic cell and monocyte progenitors in human cord blood and bone marrow.

The Journal of experimental medicine | 2015

In mice, two restricted dendritic cell (DC) progenitors, macrophage/dendritic progenitors (MDPs) and common dendritic progenitors (CDPs), demonstrate increasing commitment to the DC lineage, as they sequentially lose granulocyte and monocyte potential, respectively. Identifying these progenitors has enabled us to understand the role of DCs and monocytes in immunity and tolerance in mice. In humans, however, restricted monocyte and DC progenitors remain unknown. Progress in studying human DC development has been hampered by lack of an in vitro culture system that recapitulates in vivo DC hematopoiesis. Here we report a culture system that supports development of CD34(+) hematopoietic stem cell progenitors into the three major human DC subsets, monocytes, granulocytes, and NK and B cells. Using this culture system, we defined the pathway for human DC development and revealed the sequential origin of human DCs from increasingly restricted progenitors: a human granulocyte-monocyte-DC progenitor (hGMDP) that develops into a human monocyte-dendritic progenitor (hMDP), which in turn develops into monocytes, and a human CDP (hCDP) that is restricted to produce the three major DC subsets. The phenotype of the DC progenitors partially overlaps with granulocyte-macrophage progenitors (GMPs). These progenitors reside in human cord blood and bone marrow but not in the blood or lymphoid tissues.

Pubmed ID: 25687283 RIS Download

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Associated grants

  • Agency: NINDS NIH HHS, United States
    Id: F31 NS084776
  • Agency: NCRR NIH HHS, United States
    Id: UL1RR024143
  • Agency: NIAID NIH HHS, United States
    Id: 1U19AI111825-01
  • Agency: NCRR NIH HHS, United States
    Id: UL1 RR024143
  • Agency: NIAID NIH HHS, United States
    Id: AI101251
  • Agency: Howard Hughes Medical Institute, United States
  • Agency: NINDS NIH HHS, United States
    Id: NS084776
  • Agency: NIAID NIH HHS, United States
    Id: U19 AI111825
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI013013
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI101251
  • Agency: NIAID NIH HHS, United States
    Id: AI13013

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