A comprehensive model of the spatio-temporal stem cell and tissue organisation in the intestinal crypt.
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.
Interdisciplinary Centre for Bioinformatics, University Leipzig, Leipzig, Germany. buske@izbi.uni-leipzig.de
Peter
P
Buske
Jörg
J
Galle
Nick
N
Barker
Gabriela
G
Aust
Hans
H
Clevers
Markus
M
Loeffler
D017209:Apoptosis; D049109:Cell Proliferation; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology*; D008954:Models, Biological; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*; D051153:Wnt Proteins / Q000378:metabolism
D051880:Receptors, Notch; D051153:Wnt Proteins
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