Prospective isolation of human clonogenic common myeloid progenitors.
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-3R alpha 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.
Manz
Markus G
MG
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. manz@irb.unisi.ch
Miyamoto
Toshihiro
T
Akashi
Koichi
K
Weissman
Irving L
IL
D000328:Adult; D019070:Cell Lineage; D005312:Fetal Blood / Q000166:cytology; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction