Please use this identifier to cite or link to this item: https://doi.org/10.1242/dev.104976
Title: Stroma provides an intestinal stem cell niche in the absence of epithelial Wnts
Authors: Kabiri Z. 
Greicius G. 
Madan B. 
Biechele S.
Zhong Z.
Zaribafzadeh H.
Edison 
Aliyev J. 
Wu Y.
Bunte R. 
Williams B.O.
Rossant J.
Virshup D.M. 
Keywords: cell protein
r spondin 3 protein
unclassified drug
Wnt protein
animal cell
article
cell differentiation
cell proliferation
cell regeneration
endoplasmic reticulum
ex vivo study
homeostasis
intestine epithelium cell
mouse
nonhuman
Paneth cell
priority journal
protein secretion
radiation injury
signal transduction
stem cell niche
stroma cell
Animals
Apoptosis
Cell Proliferation
Endoplasmic Reticulum
Epithelial Cells
Epithelium
Fibroblasts
Gene Deletion
HEK293 Cells
Homeostasis
Humans
Intestines
Membrane Proteins
Mice
Mice, Inbred C57BL
Mice, Knockout
Oligonucleotide Array Sequence Analysis
Paneth Cells
Signal Transduction
Stem Cell Niche
Stem Cells
Stromal Cells
Thrombospondins
Wnt Proteins
Issue Date: 2014
Publisher: Company of Biologists Ltd
Citation: Kabiri Z., Greicius G., Madan B., Biechele S., Zhong Z., Zaribafzadeh H., Edison, Aliyev J., Wu Y., Bunte R., Williams B.O., Rossant J., Virshup D.M. (2014). Stroma provides an intestinal stem cell niche in the absence of epithelial Wnts. Development (Cambridge) 141 (11) : 2206-2215. ScholarBank@NUS Repository. https://doi.org/10.1242/dev.104976
Abstract: Wnt/?-catenin signaling supports intestinal homeostasis by regulating proliferation in the crypt. Multiple Wnts are expressed in Paneth cells as well as other intestinal epithelial and stromal cells. Ex vivo, Wnts secreted by Paneth cells can support intestinal stem cells when Wnt signaling is enhanced with supplemental R-Spondin 1 (RSPO1). However, in vivo, the source of Wnts in the stem cell niche is less clear. Genetic ablation of Porcn, an endoplasmic reticulum resident O-acyltransferase that is essential for the secretion and activity of all vertebrate Wnts, confirmed the role of intestinal epithelial Wnts in ex vivo culture. Unexpectedly, mice lacking epithelial Wnt activity (PorcnDel/Villin-Cre mice) had normal intestinal proliferation and differentiation, as well as successful regeneration after radiation injury, indicating that epithelial Wnts are dispensable for these processes. Consistent with a key role for stroma in the crypt niche, intestinal stromal cells endogenously expressing Wnts and Rspo3 support the growth of PorcnDel organoids ex vivo without RSPO1 supplementation. Conversely, increasing pharmacologic PORCN inhibition, affecting both stroma and epithelium, reduced Lgr5 intestinal stem cells, inhibited recovery from radiation injury, and at the highest dose fully blocked intestinal proliferation. We conclude that epithelial Wnts are dispensable and that stromal production of Wnts can fully support normal murine intestinal homeostasis. © 2014. Published by The Company of Biologists Ltd.
Source Title: Development (Cambridge)
URI: https://scholarbank.nus.edu.sg/handle/10635/175323
ISSN: 0950-1991
DOI: 10.1242/dev.104976
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