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 m...

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Main Authors: Peter Buske, Jörg Galle, Nick Barker, Gabriela Aust, Hans Clevers, Markus Loeffler
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS Computational Biology
Online Access:http://europepmc.org/articles/PMC3017108?pdf=render
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author Peter Buske
Jörg Galle
Nick Barker
Gabriela Aust
Hans Clevers
Markus Loeffler
author_facet Peter Buske
Jörg Galle
Nick Barker
Gabriela Aust
Hans Clevers
Markus Loeffler
author_sort Peter Buske
collection DOAJ
description 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.
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spelling doaj.art-b719dc722ed64f1c995aec9525e3ec6d2022-12-21T22:50:54ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582011-01-0171e100104510.1371/journal.pcbi.1001045A comprehensive model of the spatio-temporal stem cell and tissue organisation in the intestinal crypt.Peter BuskeJörg GalleNick BarkerGabriela AustHans CleversMarkus LoefflerWe 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.http://europepmc.org/articles/PMC3017108?pdf=render
spellingShingle Peter Buske
Jörg Galle
Nick Barker
Gabriela Aust
Hans Clevers
Markus Loeffler
A comprehensive model of the spatio-temporal stem cell and tissue organisation in the intestinal crypt.
PLoS Computational Biology
title A comprehensive model of the spatio-temporal stem cell and tissue organisation in the intestinal crypt.
title_full A comprehensive model of the spatio-temporal stem cell and tissue organisation in the intestinal crypt.
title_fullStr A comprehensive model of the spatio-temporal stem cell and tissue organisation in the intestinal crypt.
title_full_unstemmed A comprehensive model of the spatio-temporal stem cell and tissue organisation in the intestinal crypt.
title_short A comprehensive model of the spatio-temporal stem cell and tissue organisation in the intestinal crypt.
title_sort comprehensive model of the spatio temporal stem cell and tissue organisation in the intestinal crypt
url http://europepmc.org/articles/PMC3017108?pdf=render
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