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.
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. manz@irb.unisi.ch
Markus G
MG
Manz
Toshihiro
T
Miyamoto
Koichi
K
Akashi
Irving L
IL
Weissman
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