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A clonogenic common myeloid progenitor that gives rise to all myeloid lineages

Nature volume 404, pages 193–197 (2000)Cite this article

Abstract

Haematopoietic stem cells give rise to progeny that progressively lose self-renewal capacity and become restricted to one lineage1,2. The points at which haematopoietic stem cell-derived progenitors commit to each of the various lineages remain mostly unknown. We have identified a clonogenic common lymphoid progenitor that can differentiate into T, B and natural killer cells but not myeloid cells3. Here we report the prospective identification, purification and characterization, using cell-surface markers and flow cytometry, of a complementary clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Common myeloid progenitors give rise to either megakaryocyte/erythrocyte or granulocyte/macrophage progenitors. Purified progenitors were used to provide a first-pass expression profile of various haematopoiesis-related genes. We propose that the common lymphoid progenitor and common myeloid progenitor populations reflect the earliest branch points between the lymphoid and myeloid lineages, and that the commitment of common myeloid progenitors to either the megakaryocyte/erythrocyte or the granulocyte/macrophage lineages are mutually exclusive events.

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Figure 1: Identification of myeloid progenitors in mouse bone marrow.
Figure 2: Morphology of day-7 colonies derived from sorted myeloid progenitors.
Figure 3: Lineage relationships among the myeloid progenitor subsets.
Figure 4: Differential expression of transcription factors in various stages of myeloid and lymphoid progenitors.
Figure 5: Proposed model of major haematopoietic maturation pathways from HSCs.

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Acknowledgements

This work was supported by a USPHS US Public Health Service grant to I.L.W. and a 1997 Jose Carreras International Leukemia Foundation grant to K.A. D.T. is supported by a National Institute of Allergy and Infectious Diseases Training Grant. We thank S.-I. Nishikawa for anti-IL-7R antibody, J. Domen for H2K- BCL-2 mice and helpful discussions, D. Wright and A. Kiger for critical evaluation of the manuscript, L. Jerabek for excellent laboratory management and assistance with animal procedures, V. Braunstein for antibody preparation, the Stanford FACS facility for flow cytometer maintenance, and L. Hidalgo and B. Lavarro for animal care.

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  1. Koichi Akashi

    Present address: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts, 02115, USA

  2. Koichi Akashi and David Traver: These authors contributed equally to this work

  3. Correspondence and requests for materials should be addressed to K.A.

Authors and Affiliations

  1. Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, 94305, California, USA

    Koichi Akashi, David Traver, Toshihiro Miyamoto & Irving L. Weissman

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  1. Koichi Akashi
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Correspondence to Koichi Akashi.

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Akashi, K., Traver, D., Miyamoto, T. et al. A clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Nature 404, 193–197 (2000). https://doi.org/10.1038/35004599

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