Prospective isolation of human clonogenic common myeloid progenitors

MG Manz, T Miyamoto, K Akashi… - Proceedings of the …, 2002 - National Acad Sciences
MG Manz, T Miyamoto, K Akashi, IL Weissman
Proceedings of the National Academy of Sciences, 2002National Acad Sciences
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+ …
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-3Rα 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.
National Acad Sciences