DIFFERENTIAL EXPRESSION OF ID GENES IN MULTIPOTENT MYELOID PROGENITORCELLS - ID-1 IS INDUCED BY EARLY-ACTING AND LATE-ACTING CYTOKINES WHILE ID-2 IS SELECTIVELY INDUCED BY CYTOKINES THAT DRIVE TERMINAL GRANULOCYTIC DIFFERENTIATION

Hematopoietic development is regulated by a complex mixture of cytokin e growth factors that guide growth and differentiation of progenitor c ell populations at different stages in their development. The genetic programs that drive this process are controlled at the molecular level by the type and number of transcriptional regulators coexpressed in t he cell. Both positive- and negative-acting helix-loop-helix transcrip tion factors are expressed during hematopoietic development, with the Id-type transdominant negative regulators controlling the net helix-lo op-helix activation potential in the cell at any given time. It has be en demonstrated that some of these Id factors are involved in the chec kpoint at which undifferentiated progenitor cells make the commitment to terminal maturation. Therefore, we sought to determine whether thes e Id family factors are selectively induced or extinguished by cytokin es that act at different points during hematopoiesis. NFS-60, a myeloi d progenitor line that proliferates in response to multiple cytokines, was stimulated by treatment with SCF, IL-3, IL-6, C-CSF, and erythrop oietin. Id-1 expression correlated rightly with cellular proliferation : it declined when growth factor stimulation was withdrawn and was qui ckly induced whenever the cell began to proliferate. The regulation of Id-2 was more complex: its expression was slightly upregulated in fac tor-deprived cells but only strongly reinduced after extended exposure to cytokines that drive granulocytic differentiation (IL-6, G-CSF, an d TGF beta 1). These data support a cell-cycle regulatory role for Id- 1 in multipotent myeloid progenitor cells and a role for Id-2 during t erminal granulocytic differentiation. J. Cell. Biochem. 71:277-285, 19 98. (C) 1998 Wiley-Liss, Inc.