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

TY - JOUR

T1 - A comprehensive model of the spatio-temporal stem cell and tissue organisation in the intestinal crypt

AU - Buske, P.

AU - Galle, J.

AU - Barker, N.

AU - Aust, G.

AU - Clevers, H.

AU - Loeffler, M.

N1 - Reporting year: 2011

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pcbi.1001045

DO - 10.1371/journal.pcbi.1001045

M3 - Article

SN - 1553-734X

VL - 7

SP - 1001045

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 1

ER -