Stem cells are an important component of tissue architecture. Identifying the exact regulatory circuits that can stably maintain tissue constant size through regulated cell turnover is critical for our basic understanding of multicellular organisms. It is equally critical for figuring out how tumors circumvent this regulation, thus providing targets for treatment. Despite great strides in the understanding of the molecular components of stem-cell regulation, the overall mechanisms orchestrating tissue homeostasis are still far from being understood. Typically, tissue contains the stem cells, transit amplifying cells, and terminally differentiated cells. Each of these cell types can potentially secrete regulatory factors and/or respond to factors secreted by other types. The feedback can be positive or negative in nature. This gives rise to a bewildering array of possible networks that drive tissue regulation. In this talk Komarova will describe a novel stochastic method of studying stem cell lineage regulation, which allows us to identify possible numbers, types, and directions of control loops that are compatible with stability, keep the variance low, and possess a certain degree of robustness. She will also discuss evolutionary optimization and cancer-delaying role of stem cells.

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