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@article{1347666,
author = {Janeckova, L and Fafílek, Bohumil and Krausova, M and Horazna, M and Vojtechova, M and AlberichandJorda, M and Sloncova, E and Galuskova, K and Sedlacek, R and Anderova, M and Korinek, V},
article_location = {MALDEN},
article_number = {3},
doi = {http://dx.doi.org/10.1002/dvg.22922},
keywords = {beta-catenin; Cre; loxP; gene targeting; gut; Wnt pathway; TCF; LEF transcription factors},
language = {eng},
issn = {1526-954X},
journal = {GENESIS},
title = {Wnt Signaling Inhibition Deprives Small Intestinal Stem Cells of Clonogenic Capacity},
url = {http://dx.doi.org/10.1002/dvg.22922},
volume = {54},
year = {2016}
}
TY - JOUR
ID - 1347666
AU - Janeckova, L - Fafílek, Bohumil - Krausova, M - Horazna, M - Vojtechova, M - Alberich-Jorda, M - Sloncova, E - Galuskova, K - Sedlacek, R - Anderova, M - Korinek, V
PY - 2016
TI - Wnt Signaling Inhibition Deprives Small Intestinal Stem Cells of Clonogenic Capacity
JF - GENESIS
VL - 54
IS - 3
SP - 101-114
EP - 101-114
PB - WILEY-BLACKWELL
SN - 1526954X
KW - beta-catenin
KW - Cre
KW - loxP
KW - gene targeting
KW - gut
KW - Wnt pathway
KW - TCF
KW - LEF transcription factors
UR - http://dx.doi.org/10.1002/dvg.22922
L2 - http://dx.doi.org/10.1002/dvg.22922
N2 - 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 -catenin-TCF4-responsive genes. Interestingly, suppression of Wnt/-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 -catenin-Tcf-mediated transcription. genesis 54:101-114, 2016. (c) 2016 The Authors genesis Published by Wiley Periodicals, Inc.
ER -
JANECKOVA, L, Bohumil FAFÍLEK, M KRAUSOVA, M HORAZNA, M VOJTECHOVA, M ALBERICH-JORDA, E SLONCOVA, K GALUSKOVA, R SEDLACEK, M ANDEROVA and V KORINEK. Wnt Signaling Inhibition Deprives Small Intestinal Stem Cells of Clonogenic Capacity. \textit{GENESIS}. MALDEN: WILEY-BLACKWELL, 2016, vol.~54, No~3, p.~101-114. ISSN~1526-954X. Available from: https://dx.doi.org/10.1002/dvg.22922.
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