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Revised map of the human progenitor hierarchy shows the origin of macrophages and dendritic cells in early lymphoid development

Nature Immunology volume 11, pages 585–593 (2010)Cite this article

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Abstract

The classical model of hematopoiesis posits the segregation of lymphoid and myeloid lineages as the earliest fate decision. The validity of this model in the mouse has been questioned; however, little is known about the lineage potential of human progenitors. Here we provide a comprehensive analysis of the human hematopoietic hierarchy by clonally mapping the developmental potential of seven progenitor classes from neonatal cord blood and adult bone marrow. Human multilymphoid progenitors, identified as a distinct population of Thy-1neg–loCD45RA+ cells in the CD34+CD38− stem cell compartment, gave rise to all lymphoid cell types, as well as monocytes, macrophages and dendritic cells, which indicated that these myeloid lineages arise in early lymphoid lineage specification. Thus, as in the mouse, human hematopoiesis does not follow a rigid model of myeloid-lymphoid segregation.

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Figure 1: Sorting of human progenitors.
Figure 2: Clonal analysis of candidate cord blood and bone marrow progenitor fractions.
Figure 3: Clonal analysis of human MLPs.
Figure 4: Differentiation of human progenitors into mature DCs.
Figure 5: In vivo lineage potential of human progenitors.
Figure 6: Lineage-specific gene expression in human progenitors.

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Acknowledgements

We thank K. Moore and the obstetrics unit of Trillium Hospital for providing cord blood samples; P.A. Penttilä, S. Zhao and L. Jamieson at the SickKids-UHN Flow Cytometry Facility for sorting; and N. Iscove for critical review of the manuscript. Supported by the Canadian Institutes for Health Research (F.N. and S.D.), the Stem Cell Network of Canadian National Centres of Excellence, the Canadian Cancer Society Research Institute, the Terry Fox Foundation, Genome Canada through the Ontario Genomics Institute, the Ontario Institute for Cancer Research, the province of Ontario, the Leukemia and Lymphoma Society, Canada Research and the Ontario Ministry of Health and Long Term Care. The views expressed here do not necessarily reflect those of the Ontario Ministry of Health and Long Term Care.

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Author notes

  1. Sergei Doulatov and Faiyaz Notta: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Stem Cell and Developmental Biology, Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada

    Sergei Doulatov, Faiyaz Notta, Kolja Eppert & John E Dick

  2. Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada

    Sergei Doulatov, Faiyaz Notta, Kolja Eppert & John E Dick

  3. Departments of Medical Biophysics and Immunology, Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada

    Linh T Nguyen & Pamela S Ohashi

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Contributions

S.D. and F.N. designed and did experiments; S.D. wrote the manuscript; K.E. analyzed microarray data; L.T.N. did DC population expansion experiments; and P.S.O. and J.E.D. supervised the study and wrote the manuscript.

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Correspondence to John E Dick.

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Doulatov, S., Notta, F., Eppert, K. et al. Revised map of the human progenitor hierarchy shows the origin of macrophages and dendritic cells in early lymphoid development. Nat Immunol 11, 585–593 (2010). https://doi.org/10.1038/ni.1889

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