In this case, the proportion of a given phenotype would reflect the probability of an individual cell to reach that phenotype. Alternatively, cell-to-cell interactions Ruxolitinib 941678-49-5 between the cells in the population can influence the noise dynamics of each individual cell either by modulating the noise in general or by increasing or decreasing the probability to reach a given phenotypic state. In the present study, we set out to investigate the second hypothesis. An obvious and well-known manifestation of the non-genetic cell individuality in culture is the unique migration properties of each cell. Migration can induce fluctuations of local cell SCH772984 density and create spatial arrangements at the population level. It is likely that intracellular fluctuations and variations in cell-to-cell interactions may interfere in a non-trivial way. Very little is known about the outcome of these interactions and their potential role in cell fate decisions. We have previously observed that cell density can increase the gene expression noise and induce epigenetic effects leading to stable changes in gene expression. We have also observed that cells with stem-like characteristics tend to appear in low density regions of myogenic cell populations suggesting that the fate choice between a stem cell-like and a differentiation committed phenotype is controlled by the appropriate local microenvironment generated by the cells themselves. In the present study, we investigated the relationship between the phenotypic switch and spatial distribution in clonal populations of primary muscle-derived cells using cell culture experiments and computer simulations. We show that proliferating myogenic cells in culture can fluctuate between phenotypic states under the effect of the local microenvironment. Computer simulations suggest that the phenotypic fluctuations follow a bistable dynamics driven by a microenvironmental context-dependent intracellular noise. The microenvironment is shaped by the cells themselves because their motion generates non-random cell interactions. In this way each cell contributes to put together its own microenvironment that in turn stimulates the fluctuation between the phenotypes until a state with low noise is found. We used populations of primary mononuclear cells isolated from human muscle that contain progenitor cells with high proliferative capacity that are usually considered as definitively committed to muscle fate. These cells express myogenic markers believed to specify definitive cell commitment such as CD56.