Evidence for a Crucial Role of Paneth Cells in Mediating the Intestinal Response to Injury123. (20th March 2013)

• Record Type: Journal Article
• Authors: Parry, Lee; Young, Madeleine; El Marjou, Fatima; Clarke, Alan R.
• Is Part Of: Stem cells. Volume 31:Number 4(2013:Apr.)
• Page Start: 776
• Page End: 785
• Publication Date: 2013-03-20
• Subjects: Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.1326
• Languages: English
• ISSNs: 1066-5099

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>The identification of the intestinal stem cell (ISC) markers <italic>Lgr5</italic> and <italic>Bmi‐1</italic> has furthered our understanding of how they accomplish homeostasis in this rapidly self‐renewing tissue. Recent work indicates that these markers identify a cycling <italic>Lgr5</italic><sup>+</sup> ISC which can be replaced by a quiescent Bmi‐1<sup>+</sup> 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 <italic>Lgr5</italic> 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. S<sc>TEM</sc> C<sc>ELLS</sc><italic>2013;31:776–785</italic></p> </abstract>