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J Exp Med. 2015 Mar 9;212(3):385-99. doi: 10.1084/jem.20141442. Epub 2015 Feb 16.

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

Author information

1
Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032.
2
Laboratory of Molecular Immunology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065.
3
Case Western Reserve University, Cleveland, OH 44106.
4
Laboratory of Molecular Immunology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065 Laboratory of Molecular Immunology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065 kl2529@columbia.edu nussen@rockefeller.edu.
5
Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032 kl2529@columbia.edu nussen@rockefeller.edu.

Abstract

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.

PMID:
25687283
PMCID:
PMC4354373
DOI:
10.1084/jem.20141442
[Indexed for MEDLINE]
Free PMC Article

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