A comprehensive model of the spatio-temporal stem cell and tissue organisation in the intestinal crypt

P. Buske, J. Galle, N. Barker, G. Aust, H. Clevers, M. Loeffler

Research output: Contribution to journal/periodicalArticleScientificpeer-review

331 Downloads (Pure)

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 organisation.
Original languageEnglish
Pages (from-to)1001045
JournalPLoS Computational Biology
Volume7
Issue number1
DOIs
Publication statusPublished - 2011

Fingerprint Dive into the research topics of 'A comprehensive model of the spatio-temporal stem cell and tissue organisation in the intestinal crypt'. Together they form a unique fingerprint.

  • Cite this