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Tissue Specific Stem Cells
Article first published online: 24 MAR 2013
Copyright © 2013 AlphaMed Press
Volume 31, Issue 4, pages 776–785, April 2013
How to Cite
Parry, L., Young, M., El Marjou, F. and Clarke, A. R. (2013), Evidence for a Crucial Role of Paneth Cells in Mediating the Intestinal Response to Injury. STEM CELLS, 31: 776–785. doi: 10.1002/stem.1326
Author contributions: L.P.: conception and design, collection and/or assembly of data, data analysis and interpretation, and manuscript writing; M.Y.: collection and/or assembly of data; F.E.M.: provision of study material; A.C.: conception and design, data analysis and interpretation, and final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLS EXPRESS January 17, 2013.
- Issue published online: 24 MAR 2013
- Article first published online: 24 MAR 2013
- Manuscript Accepted: 17 DEC 2012
- Manuscript Received: 29 JUN 2012
- Cancer Research UK
- Stem cells;
- Paneth cells;
- Genetically modified animals
The identification of the intestinal stem cell (ISC) markers Lgr5 and Bmi-1 has furthered our understanding of how they accomplish homeostasis in this rapidly self-renewing tissue. Recent work indicates that these markers identify a cycling Lgr5+ ISC which can be replaced by a quiescent Bmi-1+ ISC. Currently, there is little data on how these cells interact to control intestinal crypt homeostasis and regeneration. This interaction likely involves other differentiated cells within the niche as it has previously been demonstrated that the “stemness” of the Lgr5 ISC is closely tied to the presence of their neighboring Paneth cells. To investigate this, we used two conditional mouse models to delete the transcription factor β-catenin within the intestinal crypt. Critically these differ in their ability to drive recombination within Paneth cells and therefore allow us to compare the effect of deleting the majority of active ISCs in the presence or absence of the Paneth cells. After gene deletion, the intestines in the model in which Paneth cells were retained showed a rapid recovery and repopulation of the crypt-villus axis presumably from either a spared ISC or the hypothetical quiescent ISCs. However, in the absence of Paneth cells the recovery ability was compromised resulting in complete loss of intestinal epithelial integrity. This data indicates that the Paneth cells play a crucial role within the in vivo ISC niche in aiding recovery following substantial insult. STEM CELLS 2013;31:776–785