Cellular Decision Making and Biological Noise: From Microbes to Mammals

Department of Systems Biology-Unit 950, The University of Texas MD Anderson Cancer Center, 7435 Fannin Street, Houston, TX 77054, USA.
Cell (Impact Factor: 32.24). 03/2011; 144(6):910-25. DOI: 10.1016/j.cell.2011.01.030
Source: PubMed


Cellular decision making is the process whereby cells assume different, functionally important and heritable fates without an associated genetic or environmental difference. Such stochastic cell fate decisions generate nongenetic cellular diversity, which may be critical for metazoan development as well as optimized microbial resource utilization and survival in a fluctuating, frequently stressful environment. Here, we review several examples of cellular decision making from viruses, bacteria, yeast, lower metazoans, and mammals, highlighting the role of regulatory network structure and molecular noise. We propose that cellular decision making is one of at least three key processes underlying development at various scales of biological organization.

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    • "However, a mechanism linking them definitively has not yet been identified. Control of transcriptional noise may be permissive for cell fate decisions, and therefore, tight regulation of transcriptional consistency may be required for full commitment to a phenotype [8]. The goal of this study was to identify distinctive patterns of H3K4me3 peak breadth within a narrower region around TSSs and determine if H3K4me3 breadth specifically at TSSs represented an independent variable of transcription regulation , a topic not previously investigated in diseases. "
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    • "Cells of a clonal population in a homogeneous medium may show large variations in size, morphology, molecular components, and activity. This cellular heterogeneity plays important functional roles in processes such as development and cell differentiation, cell decisions, virus infection, apoptosis, and cancer12345. Cell-to-cell variability is originated by differences in gene activity, which confers each cell a unique " expression fingerprint " with possible phenotypic consequences. "
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    ABSTRACT: Gene expression activity is heterogeneous in a population of isogenic cells. Identifying the molecular basis of this variability will improve our understanding of phenomena like tumor resistance to drugs, virus infection, or cell fate choice. The complexity of the molecular steps and machines involved in transcription and translation could introduce sources of randomness at many levels, but a common constraint to most of these processes is its energy dependence. In eukaryotic cells, most of this energy is provided by mitochondria. A clonal population of cells may show a large variability in the number and functionality of mitochondria. Here, we discuss how differences in the mitochondrial content of each cell contribute to heterogeneity in gene products. Changes in the amount of mitochondria can also entail drastic alterations of a cell's gene expression program, which ultimately leads to phenotypic diversity. Also watch the Video Abstract.
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    • "Such fluctuations lead to macroscopic effects in a diverse array of processes. In differentiation, the resulting noise plays a central role in cell fate determination and can allow clonal populations of differentiating cells to achieve distinct final states [3] [4]. Noise can also produce spontaneous transitions, whereby it causes a system to switch from one stable state to another, often producing a significant change of phenotype or function. "
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