Wnt signaling inhibition deprives small intestinal stem cells of clonogenic capacity
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F16%3A00457224" target="_blank" >RIV/68378050:_____/16:00457224 - isvavai.cz</a>
Alternative codes found
RIV/68378041:_____/16:00457224
Result on the web
<a href="http://dx.doi.org/10.1002/dvg.22922" target="_blank" >http://dx.doi.org/10.1002/dvg.22922</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/dvg.22922" target="_blank" >10.1002/dvg.22922</a>
Alternative languages
Result language
angličtina
Original language name
Wnt signaling inhibition deprives small intestinal stem cells of clonogenic capacity
Original language description
The Wnt pathway plays a crucial role in self-renewal and differentiation of cells in the adult gut. In the present study, we revealed the functional consequences of inhibition of canonical Wnt signaling in the intestinal epithelium. The study was based on generation of a novel transgenic mouse strain enabling inducible expression of an N-terminally truncated variant of nuclear Wnt effector T cell factor 4 (TCF4). The TCF4 variant acting as a dominant negative (dn) version of wild-type (wt) TCF4 protein decreased transcription of β-catenin-TCF4-responsive genes. Interestingly, suppression of Wnt/β-catenin signaling affected asymmetric division of intestinal stem cells (ISCs) rather than proliferation. ISCs expressing the transgene underwent several rounds of division but lost their clonogenic potential and migrated out of the crypt. Expression profiling of crypt cells revealed that besides ISC-specific markers, the dnTCF4 production downregulated expression levels of epithelial genes produced in other crypt cells including markers of Paneth cells. Additionally, in Apc conditional knockout mice, dnTCF activation efficiently suppressed growth of Apc-deficient tumors. In summary, the generated mouse strain represents a convenient tool to study cell-autonomous inhibition of β-catenin-Tcf-mediated transcription. This article is protected by copyright. All rights reserved.
Czech name
—
Czech description
—
Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
EB - Genetics and molecular biology
OECD FORD branch
—
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Genesis
ISSN
1526-954X
e-ISSN
—
Volume of the periodical
54
Issue of the periodical within the volume
3
Country of publishing house
US - UNITED STATES
Number of pages
14
Pages from-to
101-114
UT code for WoS article
000373060400001
EID of the result in the Scopus database
—