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Dynamische Kontrolle der zellulären Reprogrammierung von Physarum polycephalum als Modell der Differenzierung von Stammzellen.
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The Physarum polycephalum plasmodium is a macroscopic multinucleate single cell with stem cell-like properties. It contains a naturally synchronous population of nuclei which provides unique experimental options for systems-oriented analyses of reprogramming at the single cell level.
During its developmental cycle, Physarum can differentiate into seven distinct cell types, each with a specific morphology, function and gene expression pattern. Differentiation is under the control of environmental signals. These cell types occur in temporal order instead of developing in parallel to build a body as it is the case in multicellular organisms (animals or plants).
We investigate how the plasmodium loses its unlimited replicative potential and is irreversibly committed to sporulation by taking one of alternative developmental pathways. Differentiation can be experimentally triggered by a brief pulse of far-red light. By systematic genetic screening and by characterisation of the obtained differentiation control mutants with suitable techniques for quantitative analysis of transcripts (mRNAs) and proteins we reconstruct the regulatory network that controls cellular reprogramming and analyse its functional dynamics. These studies are preformed at the single cell level, as identically treated cells from a clonal population take alternative pathways to differentiate. Specifically, we focus on the reconstruction of the Waddington-type quasi-potential landscape of cellular reprogramming and its genetic control through a combination of experimental and computational techniques.
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