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a comprehensive model of the spatio-temporal stem cell and tissue organisation in the intestinal crypt全面的时空模型肠隐窝干细胞和组织机构
A Comprehensive Model of the Spatio-Temporal Stem
Cell and Tissue Organisation in the Intestinal Crypt
1. ¨ 1. 2 3 2 1,4
Peter Buske *, Jorg Galle , Nick Barker , Gabriela Aust , Hans Clevers , Markus Loeffler
1 Interdisciplinary Centre for Bioinformatics, University Leipzig, Leipzig, Germany, 2 Hubrecht Institute, University Medical Center, Utrecht, The Netherlands, 3 Center of
Surgery, Research Laboratories, University Leipzig, Leipzig, Germany, 4 Institute for Medical Informatics, Statistics and Epidemiology, University Leipzig, Leipzig, Germany
Abstract
We introduce a novel dynamic model of stem cell and tissue organisation in murine intestinal crypts. Integrating the
molecular, cellular and tissue level of description, this model links a broad spectrum of experimental observations
encompassing spatially confined cell proliferation, directed cell migration, multiple cell lineage decisions and clonal
competition. Using computational simulations we demonstrate that the model is capable of quantitatively describing and
predicting the dynamic behaviour of the intestinal tissue during steady state as well as after cell damage and following
selective gain or loss of gene function manipulations affecting Wnt- and Notch-signalling. Our simulation results suggest
that reversibility and flexibility of cellular decisions are key elements of robust tissue organisation of the intestine. We
predict that the tissue should be able to fully recover after complete elimination of cellular subpopulations including
subpopulations deemed to be functional stem cells. This challenges current views of tissue stem cell organisati
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