Expression of G1-phase cell cycle genes during hematopoietic lineage

Characterization of proteins that control the passage through the G1 phase of the cell cycle is of particular interest because virtually all stimuli regulating cell proliferation or differentiation act primarily during this phase. We have analyzed the G1 phase proteic machinery, including cyclin D types, cyclin-dependent kinases (CDKs) and CDK inhibitors, of cell populations obtained at different stages of hematopoietic cell lineage. In particular, five cellular phenotypes, namely CD34+ cells (which contain stem cells), BFU-E, CFU-E, CFU-GM and peripheral lymphocytes were studied as representatives of distinct differentiation pathways. The results obtained indicated that all the cellular preparations express cyclin D2 and D3, while cyclin D1, which is the major cyclin D occurring in mesenchimal tissues, is not expressed. Moreover, CDK6 (but not CDK4) was detectable in all the populations investigated. Among the CDK inhibitors studied, p18(INK4C) and p19(INK4D) signals were clearly evidentiable in the various cell types. Interestingly, high levels of p15(INK4B), a putative tumor suppressor protein, were detectable expecially in granulocyte-monocyte precursors. Our results indicate that a specific hematopoietic G1 phase machinery occurs, which is conserved during the various steps of the different maturation processes.