Markus G. Manz*, ^@, Toshihiro Miyamoto*, Koichi Akashi ¹, and Irving L. Weissman*, ^@

* Departments of Pathology and Developmental Biology, Stanford UniversitySchool of Medicine, Stanford, CA 94305; and
¹ Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115

M.G.M. and T.M. contributed equally to this work.

^@ To whom reprint requests may be addressed at: Departments of Pathology and Developmental Biology, Stanford University School of Medicine, B257 Beckman Center, Stanford, CA 94305-5428.
E-mail:   manz@irb.unisi.ch   or   irv@stanford.edu

The hierarchical development from hematopoietic stem cells to mature cells of the hematolymphoid system involves progressive loss of self-renewal capacity, proliferation ability, and lineage potentials. Here we show the prospective isolation of early developmental intermediates, the human clonogenic common myeloid progenitors and their downstream progeny, the granulocyte/macrophage and megakaryocyte/erythrocyte progenitors. All three populations reside in the lineage-negative (lin ^-) CD34 ⁺ CD38 ⁺ fraction of adult bone marrow as well as in cord blood. They are distinguishable by the expression of the IL-3Ra chain, the receptor of an early-acting hematopoietic cytokine, and CD45RA, an isoform of a phosphotyrosine phosphatase involved in negative regulation of cytokine signaling. Multipotent progenitors, early lymphoid progenitors, and the here-defined myeloid progenitors express distinct profiles of hematopoiesis-affiliated genes. The isolation of highly purified hematopoietic intermediates provides tools to better understand developmental programs
underlying normal and leukemic hematopoiesis. 

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