1A) alerts us to the fact that population-averaging techniques that involve lysing entire populations of cells of a culture or tissue specimen mask substantial information on populace distribution. ubiquitous, yet as neglected, as the inevitable heterogeneity of cell phenotypes within a populace of cells of the same cell type. Nevertheless, the implications of such cell populace heterogeneity are far reaching, and semantic questions are inevitable: if an apparently clonal populace of cells, which are, by definition, genetically identical, is usually heterogeneous and exhibits enduring cell-to-cell variations with unique cell individuality, why then do we not talk about unique cell types, or subtypes, in the population? Stem cell experts will easily identify the ontological (observe Glossary,Box 1) problem (Orkin and Zon, 2002): if a culture of stem cells, even if clonal, is actually heterogeneous to start with, be it owing to impurities introduced by unavoidable technical limitations (Enver et al., 2009) or to intrinsic diversity, as discussed here, what then is the meaning of plasticity and multipotency, Piperazine as defined as the ability of cells to generate a variety of cell types? Perhaps the process of generating and/or acquiring heterogeneity eo ipso could lie at the core of multipotency. Box 1. Glossary Attractor state.A stationary and stable network state into which a set of particular network says will eventually evolve (be attracted to). This happens because the interactions between the network elements impose constraints so that the majority of theoretically possible network says is unstable and will move towards an attractor state. Clone, or a clonal group of cells.A group of cells that contains only cells that share a common Piperazine ancestry and hence are assumed to be genetically identical. According to this definition, however, entire organisms, being derived from a zygote, would be clones. Thus, in the context of phenotypic variability, clonal, which is usually often equated with genetically identical, must be more narrowly defined (see text). Dichotomy.The partitioning of a whole entityX(a set, concept, or phenomenon) into two, and only two, subsetsAandB, that are mutually exclusive and together cover all possible elements belonging toX. Ergodicity.A property of a system or process that satisfies the ergodic hypothesis in statistical physics, according to which the average over time of a (fluctuating) quantity of the system is the same as the average at a given time over a large sample of replicates of that system (= ensemble). Extrinsic heterogeneity.Cell-to-cell variability (typically at the level of micro-heterogeneity) in a Piperazine population caused by Piperazine nonuniform environmental factors that differentially affect individual cells. Genetic heterogeneity.A property of a population (e.g. of cells) in which the genomes of the individual members (cells) are not identical for all those users and which hence contains a mixture of unique genomes. Frequently considered in tumor biology, where the genome sequence differences between the tumor cells could explain trait differences due to somatic mutations. Intrinsic heterogeneity.Cell-to-cell variability (typically at the level of micro-heterogeneity) in the absence of inhomogeneities Spp1 in the microenvironment. Most commonly explained by gene expression noise (temporal noise), but applies also to populace noise (seeFig. 3). Macro-heterogeneity.Heterogeneity of a cell population due to the presence of a variety of discretely distinct cell types or of cells in obviously distinct says, such as progenitor versus differentiated cells. Macro-heterogeneity is usually manifest as a multi-modal distribution of a traitXin a histogram of the population (observe Figs2,4). Micro-heterogeneity.Heterogeneity within an apparently uniform cell population that is thought to consist of identical cells. Micro-heterogeneity is usually manifest as the variance (spread) of a single bell-shaped distribution (observe Figs2,4). Network state at a given time point.The state of a system (network) of interacting elements (genes) that is jointly defined by all values of activities of the elements (e.g. gene expression levels) at confirmed time. The network state of the gene regulatory network is reflected in the gene expression profile thus. nongenetic (or phenotypic) heterogeneity.A house of the population (e.g. of cells) that identifies the phenotypic variability between its people, which share.