noise-driven stem cell and progenitor population dynamicsnoise-driven干细胞和祖种群动态.pdfVIP

Noise-Driven Stem Cell and Progenitor Population Dynamics 1 2,3,4 5 2 6 1 Martin Hoffmann *, Hannah H. Chang , Sui Huang , Donald E. Ingber , Markus Loeffler , Joerg Galle 1 Interdisciplinary Centre for Bioinformatics, University of Leipzig, Leipzig, Germany, 2 Vascular Biology Program, Department of Pathology and Surgery, Children’s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America, 3 Program in Biophysics, Harvard University, Boston, Massachusetts, United States of America, 4 MD-PhD Program, Harvard Medical School, Boston, Massachusetts, United States of America, 5 Institute for Biocomplexity and Informatics, University of Calgary, Calgary, Canada, 6 Institute for Medical Informatics, Statistics, and Epidemiology, University of Leipzig, Leipzig, Germany Abstract Background: The balance between maintenance of the stem cell state and terminal differentiation is influenced by the cellular environment. The switching between these states has long been understood as a transition between attractor states of a molecular network. Herein, stochastic fluctuations are either suppressed or can trigger the transition, but they do not actually determine the attractor states. Methodology/Principal Findings: We present a novel mathematical concept in which stem cell and progenitor population dynamics are described as a probabilistic process that arises from cell proliferation and small fluctuations in the state of differentiation. These state fluctuations reflect random transitions between different activation patterns of the underlying regulatory network. Importantly, the associated noise amplitudes are state-dependent and set by the environment. Their variability