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Lymphoid priming in human bone marrow begins before expression of CD10 with upregulation of L-selectin

Nature Immunology volume 13, pages 963–971 (2012)Cite this article

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Abstract

Expression of the cell-surface antigen CD10 has long been used to define the lymphoid commitment of human cells. Here we report a unique lymphoid-primed population in human bone marrow that was generated from hematopoietic stem cells (HSCs) before onset of the expression of CD10 and commitment to the B cell lineage. We identified this subset by high expression of the homing molecule L-selectin (CD62L). CD10−CD62Lhi progenitors had full lymphoid and monocytic potential but lacked erythroid potential. Gene-expression profiling placed the CD10−CD62Lhi population at an intermediate stage of differentiation between HSCs and lineage-negative (Lin−) CD34+CD10+ progenitors. CD62L was expressed on immature thymocytes, and its ligands were expressed at the cortico-medullary junction of the thymus, which suggested a possible role for this molecule in homing to the thymus. Our studies identify the earliest stage of lymphoid priming in human bone marrow.

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Figure 1: Identification of bone marrow progenitors that lack myeloid and erythroid clonogenic potential.
Figure 2: Lympho-myeloid potential of bone marrow progenitors.
Figure 3: Lineage potential of CD10− CD62Lhi cells by in vitro clonal analysis and in vivo transplantation studies.
Figure 4: CD10−CD62Lhi cells represent an intermediate stage of differentiation between HSCs and CD10+ progenitors.
Figure 5: CD10−CD62Lhi cells represent a distinct progenitor population with a unique expression profile that combines genes of HSCs and early lymphoid cells.
Figure 6: High CD62L expression and recruitment of progenitors to human thymus.

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Acknowledgements

We thank J. Scholes, F. Codrea, X. Li and S. Dandekar for technical assistance; and D. Kohn, G. Dravid, S. Sandoval and M. Corselli for advice on the manuscript. Supported by the US National Institutes of Health (P01 HL073104 and RO1 HL077912), the California Institute of Regenerative Medicine (RC1-00108 and RM1-01717 to G.M.C.; and RN1-00557-1 to H.K.A.M.), Flow Cytometry Core of the Broad Stem Cell Research Center of the University of California, Los Angeles, and the Jonsson Comprehensive Cancer Center Genomics Shared Resource of the University of California, Los Angeles.

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Authors and Affiliations

  1. Department of Pathology & Laboratory Medicine, University of California, Los Angeles, California, USA

    Lisa A Kohn, Shundi Ge, Yuhua Zhu & Gay M Crooks

  2. Division of Research Immunology & Bone Marrow Transplantation, Children's Hospital Los Angeles, Los Angeles, California, USA

    Qian-Lin Hao

  3. Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, California, USA

    Rajkumar Sasidharan & Hanna K A Mikkola

  4. Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA

    Chintan Parekh & Gay M Crooks

  5. Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, California, USA

    Hanna K A Mikkola & Gay M Crooks

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Contributions

L.A.K. designed, did and analyzed experiments and wrote the paper; Q.-L.H. designed, did and analyzed experiments, R.S. did bioinformatics analysis of microarray data; S.G. and Y.Z. assisted in experiments; C.P. did experiments; H.K.A.M. supervised bioinformatics analysis; and G.M.C. designed and analyzed experiments and wrote the paper.

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Correspondence to Gay M Crooks.

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Kohn, L., Hao, QL., Sasidharan, R. et al. Lymphoid priming in human bone marrow begins before expression of CD10 with upregulation of L-selectin. Nat Immunol 13, 963–971 (2012). https://doi.org/10.1038/ni.2405

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