Isolation of MYADM, a novel hematopoietic-associated marker gene expressedin multipotent progenitor cells and up-regulated during myeloid differentiation

A large number of hematopoietic cytokines and their receptors as well as tr anscription factors have been shown to be involved in maturation of blood c ells, However, many of the genes important for the differentiation of multi potent stent cells to specific cellular lineages are still uknown. To ident ify novel genes involved in lineage selection of myeloid cells, we have app lied differential display analysis during commitment toward granulocytes an d macrophages of an IL-3-dependent multipotent progenitor cell line, FDCP-m ix. One regulated cDNA represented a novel gene with restricted expression pattern within the hematopoietic system and was strongly up-regulated when FDCP-mix cells differentiated iu GM-CSF, G-CSF, and M-CSF. The expression a ppears to be differentiation stage-specific in myeloid cells and is absent in B and T lymphocytes. Thus we found expression in normal mouse bone marro w enriched for stem cells and multipotent progenitors (c-kit(+)Sca-1(+)Lin( -) cells), When these cells were induced to differentiate toward myeloid ce lls, MYADM was up-regulated. In contrast, during conditions known to favor the development of B cell progenitors, the gene was down-regulated. The gem , termed MYADM for myeloid-associated differentiation marker gene, shows 10 0% identity to expressed sequence tags from early mouse embryonic developme nt as well as from the mouse lung and from activated mouse macrophages. The predicted 32-kDa MYADM protein contains multiple hydrophobic putative tran smembrane segments and has several potential consensus sites for phosphoryl ation, In view of its expression pattern, MYADM could serve as a new marker gene for hematopoietic differentiation, Although the function is known, an tisense oligonucleotides were able to inhibit colony formation of c-kit(+) Lin(-) bone marrow cells, suggesting an important role for MYADM in myeloid differentiation.