Cell cycle and differentiation

The development of multicellular organisms relies on the temporal and spatial control of cell proliferation and cell growth. The relationship between cell-cycle progression and development is complex and characterized by mutual dependencies. On the level of the individual cell, this interrelationship has implications for pattern formation and cell morphogenesis. On a supercellular level, this interrelationship affects meristem function and organ growth. Often, developmental signals not only direct cell-cycle progression but also set the frame for cell-cycle regulation by determining cell-type-specific cell-cycle modes. In other cases, however, cell-cycle progression appears to be required for the further differentiation of some cell types. There are also examples in which cell cycle and differentiation seem to be controlled at the same level and progress rather independently from each other or are linked by the same regulator or pathway. Furthermore, different relationships between cell cycle and differentiation can be combined in a succession of events during development, leading to complex developmental programs.     

Some thoughts about genetics, differentiation, and malignancy.

This article deals with three related questions: (1) whether malignancy is determined by genetic or epigenetic mechanisms; (2) whether epigenetic mechanisms, as conventionally defined, actually exist; (3) what criteria are appropriate for defining dominance or recessiveness of the malignant state in cell fusion experiments.     

Cell differentiation; Cell division, growth and death

A selection of World Wide Web sites relevant to papers published in this issue of Current Opinion in Cell Biology.     

Cell survival: differences and differentiation

The regulatory mechanisms of cell survival and apoptosis are very complex in nature, implicating numerous players and signaling pathways not only in the decision-making process of surviving (or dying), but as well as in the execution of apoptosis itself. The same complex nature applies with regards to anoikis, a form of apoptosis that is largely regulated by integrin-mediated, cell-extracellular matrix interactions. However, cell survival, apoptosis and anoikis also happen to implicate further mechanistic distinctions according to the specific tissue and/or cell type concerned. Incidentally, recent studies in a particular tissue, the human intestinal epithelium, have unearthed yet another layer of complexity in the regulation of these three cellular processes, namely the implication of differentiation state-specific mechanisms. Although our understanding of the molecular underpinnings of this new concept of differentiation state-distinct regulation of cell survival, apoptosis and/or anoikis is in its infancy, there is already evidence that such principle applies as well to cell types other than intestinal epithelial cells. Further studies on the differentiation state-specific regulation of these three cellular processes, either under normal or physiopathological situations, should prove crucial in increasing our understanding of pathologies which implicate a dysregulation of apoptosis and/or anoikis - such as cancer.     

Friend leukemia cells: relationship between differentiation, clonogenicity and malignancy

Friend leukemia cells were cultured in vitro in the presence or absence of agents which induce erythroid differentiation. The cultures were harvested and the degree of differentiation determined. Clonogenicity of the cells in vitro and malignancy in vivo were determined as well. There was an inverse exponential relationship between the degree of differentiation and the clonogenicity of the culture. Differentiation was also associated with a modest decline in malignancy. Of interest was the observation that bromodeoxyuridine inhibited the biochemical manifestations of erythroid differentiation, but did not prevent the decline in clonogenicity which accompanied differentiation.