Cell type expression mediated by cell cycle events, and signaled by mitogens and growth inhibitors

Abstract

It is initially pointed out that the majority of factors that induce cell type expression in mature precursor cells are either mitogens or growth inhibitors. On the basis of available data, a theoretical model of regulation of cell type expression for each group of factors is proposed. In model A the mitogen affects the expression of cell type through the positive control of cell cycle progression, while in model B the growth inhibitor induces the negative control of cell cycle progression, which in its turn causes the cell type expression. In connection with those two models, various systems of cell type expression are classified into three groups. In model A systems, the cell lineage has an option of autotypic and allotypic cell types. The former is expressed in the absence of added mitogen, and the latter is expressed in its presence. In model B systems the cell lineage-specific cell type is expressed by the negative cell cycle control induced by the growth inhibitor. In model A-B systems both mitogen and inhibitor are needed in tandem for the expression of a cell type. The second major point made is that the expression of cell type follows the negative control of cell cycle progression even in model A systems. However, in this system the control occurs spontaneously. This suggests that the negative control is essential for cell type expression in all systems, and directly precedes the expression. In contrast, the positive control induced by exogenous mitogen is not required in the expression in model B systems or in that of autotypic cell types in model A systems. The third point is that on the basis of the hypothesis of replication-transcription coupling, proposed by Sauer and colleagues, it is speculated that the pattern of early-replicating genes may be functioning as the potential gene transcription pattern for cell type expression in precursor cells. If this pattern is perpetuated through cell generations, the original cell type specificity of the precursor cell lineage should be maintained. If this pattern is modified by the positive control of cell cycle progression in model A systems, the potential transcriptional pattern for the allotypic pathway may emerge. Furthermore, it is proposed that the realization of the potential pattern may depend on a signal, informing the completion of the negative control of cell cycle progression. Thus in all cell lineages, when the negative cell cycle control is completed, chromatin receives this signal, and the potential transcription pattern is converted into cell type differentiation.(ABSTRACT TRUNCATED AT 400 WORDS)