Transgenerational cell fate profiling

The illicit generation of tetraploid cells constitutes a prominent driver of oncogenesis, as it often precedes the development of aneuploidy and genomic instability. In addition, tetraploid (pre-)malignant cells display an elevated resistance against radio- and chemotherapy. Here, we report a strategy to preferentially kill tetraploid tumor cells based on the broad-spectrum kinase inhibitor SP600125. Live videomicroscopy revealed that SP600125 affects the execution of mitosis, impedes proper cell division and/or activates apoptosis in near-to-tetraploid, though less so in parental, cancer cells. We propose a novel graphical model to quantify the differential response of diploid and tetraploid cells to mitotic perturbators, including SP600125, which we baptized “transgenerational cell fate profiling.” We speculate that this representation constitutes a valid alternative to classical “single-cell fate” and “genealogical” profiling and, hence, may facilitate the analysis of cell fate within a heterogeneous population as well as the visual examination of cell cycle alterations.     

DIF signalling and cell fate

The DIFs are a family of secreted chlorinated molecules that control cell fate during development of Dictyostelium cells in culture and probably during normal development too. They induce stalk cell differentiation and suppress spore cell formation. The biosynthetic and inactivation pathways of DIF-1 (the major bioactivity) have been worked out. DIF-1 is probably synthesised in prespore cells and inactivated in prestalk cells, by dechlorination. Thus, each cell type tends to alter DIF-1 level so as to favour differentiation of the other cell type. This relationship leads to a model for cell-type proportioning during normal development.     

Resveratrol in cell fate decisions

Resveratrol, a polyphenolic phytoalexin, is one of the most extensively studied natural products, with wide ranging biological activity and tremendous clinical potential. First identified from fruits and plants, in particular grapes and wines, its positive effects on a variety of disease states have been unraveled over the past decade or so. Most noticeable are its anti-thrombogenic, anti-inflammatory, cardio-protective, neuro-protective, anti-aging, and cancer preventive and therapeutic activities. Recent data also indicate that depending upon the concentration/dose, resveratrol can trigger or block cell death signaling in tumor cells. Considering the heightened interest in this compound, here we present a short review on the biological activity of this remarkable compound, with a specific focus on its effects on cell survival and death signals.     

Stochastic neuronal cell fate choices

Though many neuronal cell fate decisions result in reproducible outcomes, stochastic choices often lead to spatial randomization of cell subtypes. This is often the case in sensory systems where expression of a specific sensory receptor gene is selected randomly from a set of possible outcomes. Here, we describe recent findings elucidating the mechanisms controlling color photoreceptor subtypes in flies and olfactory receptor subtypes in worms and mice. Although well-known biological concepts such as lateral signaling and promoter selection play roles in these cases, fundamental questions concerning these choice mechanisms remain.     

A twist of cell fate

Individuals carrying deleterious BRCA1 mutations typically develop basal-like rather than luminal breast cancers. In this issue of Cell Stem Cell, Proia et?al. (2011) study breast tissue from women with heterozygous BRCA1 mutations and identify molecular mechanisms that regulate mammary progenitor cell differentiation and bias toward subsequent basal-like tumor formation.     

Asymmetric cell division and cell fate in plants

A variety of approaches has recently been employed to investigate how sister cells adopt distinct fates following asymmetric divisions during plant development. Surgical and drug studies have been used to analyze asymmetric divisions during both early embryogenesis in brown algae and pollen development in tobacco. Genetic screens have been used to identify genes in Arabidopsis thaliana that are required for specific asymmetric cell divisions during pollen and root development. These studies indicate that cell polarity and division orientation are closely tied to the process of cell fate specification, and suggest that differential inheritance of determinants and positional information may both be involved in the specification of cell fates following asymmetric cell division.     

Blood cell fate changes without cell cycle transition

Comment on: Di Tullio A, et al. Cell Cycle 2012; 11:2739-46.