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A newly discovered class of human hematopoietic cells with SCID-repopulating activity

Nature Medicine volume 4, pages 1038–1045 (1998)Cite this article

Abstract

The detection of primitive hematopoietic cells based on repopulation of immune-deficient mice is a powerful tool to characterize the human stem-cell compartment. Here, we identify a newly discovered human repopulating cell, distinct from previously identified repopulating cells, that initiates multilineage hematopoiesis in NOD/SCID mice. We call such cells CD34neg- S CID r epopulating c ells, or CD34neg-SRC. CD34neg-SRC are restricted to a Lin–CD34–CD38– population without detectable surface markers for multiple lineages and CD38 or those previously associated with stem cells (HLA-DR, Thy-1 and CD34). In contrast to CD34+ subfractions, Lin–CD34–CD38– cells have low clonogenicity in short-and long-term in vitro assays. The number of CD34neg-SRC increased in short-term suspension cultures in conditions that did not maintain SRC derived from CD34+ populations, providing independent biological evidence of their distinctiveness. The identification of this newly discovered cell demonstrates complexity of the organization of the human stem-cell compartment and has important implications for clinical applications involving stem-cell transplantation.

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Figure 1: Phenotypic analysis of human Lin–CD34– hematopoietic cells.
Figure 2: Frequency analysis of Lin–CD34– cells found in human hematopoietic tissue throughout development.
Figure 3: Human cell engraftment of NOD/SCID mice transplanted at various cell doses with purified Lin–CD34– cells from cord blood.
Figure 4: Multilineage differentiation of human Lin–CD34– cells in NOD/SCID mice.
Figure 5: Capacity of Lin–CD34–, Lin–CD34–CD38–, Lin–CD34–CD38+ and Lin–CD34+CD38– cells cell fractions to engraft NOD/SCID after ex vivo culture.

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Acknowledgements

We thank L. McWhirter for providing cord blood and fetal specimens, H. Messner and N. Jamal for providing bone marrow and peripheral blood samples, G. Knowles for technical support in the flow cytometric analysis, and R. Phillips, A. Bernstein, N. Iscove, R. McInnes and members of the laboratory for reviewing the manuscript. This work was supported by grants to J.E.D. from the Medical Research Council of Canada (MRC), the National Cancer Institute of Canada (NCIC) with funds from the Canadian Cancer Society, the Canadian Genetic Diseases Network of the National Centers of Excellence, an MRC Scientist award (J.E.D.), postdoctoral fellowships from the NCIC (M.B.), and the Human Frontier Science Organization Program (D.B.).

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Author notes

  1. Mickie Bhatia

    Present address: The John. P. Robarts Research Institute, Gene Therapy and Molecular Virology, 100 Perth Drive, London, Ontario, N6A 5K8

  2. Dominique Bonnet

    Present address: Coriell Institute for Medical Research, 401 Haddon Avenue, 08103, Camden, New Jersey

  3. M.B and D.B. contributed equally to this work

Authors and Affiliations

  1. Programs in Cancer/Blood and Developmental Biology, Research Institute, Hospital for Sick Children, 555 University Avenue, Toronto, M5G 1X8, Ontario, Canada

    Mickie Bhatia, Dominique Bonnet, Barbara Murdoch, Olga I. Gan & John E. Dick

  2. Department of Molecular and Medical Genetics, University of Toronto,

    Mickie Bhatia, Dominique Bonnet, Barbara Murdoch, Olga I. Gan & John E. Dick

  3. Department of Mircobiology and Immunology, University of Western Ontario,

    Mickie Bhatia

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  1. Mickie Bhatia
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Correspondence to John E. Dick.

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Bhatia, M., Bonnet, D., Murdoch, B. et al. A newly discovered class of human hematopoietic cells with SCID-repopulating activity. Nat Med 4, 1038–1045 (1998). https://doi.org/10.1038/2023

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