Show simple item record

dc.contributor.author
Borrelli, Costanza
dc.contributor.author
Valenta, Tomas
dc.contributor.author
Handler, Kristina
dc.contributor.author
Vélez, Karelia
dc.contributor.author
Gurtner, Alessandra
dc.contributor.author
Moro, Giulia
dc.contributor.author
Lafzi, Atefeh
dc.contributor.author
de Vargas Roditi, Laura
dc.contributor.author
Hausmann, George
dc.contributor.author
Arnold, Isabelle C.
dc.contributor.author
Moor, Andreas E.
dc.contributor.author
Basler, Konrad
dc.date.accessioned
2021-03-16T21:41:18Z
dc.date.available
2021-03-14T05:26:24Z
dc.date.available
2021-03-16T21:41:18Z
dc.date.issued
2021
dc.identifier.issn
2041-1723
dc.identifier.other
10.1038/s41467-021-21591-9
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/474342
dc.identifier.doi
10.3929/ethz-b-000474342
dc.description.abstract
The homeostasis of the gut epithelium relies upon continuous renewal and proliferation of crypt-resident intestinal epithelial stem cells (IESCs). Wnt/β-catenin signaling is required for IESC maintenance, however, it remains unclear how this pathway selectively governs the identity and proliferative decisions of IESCs. Here, we took advantage of knock-in mice harboring transgenic β-catenin alleles with mutations that specifically impair the recruitment of N- or C-terminal transcriptional co-factors. We show that C-terminally-recruited transcriptional co-factors of β-catenin act as all-or-nothing regulators of Wnt-target gene expression. Blocking their interactions with β-catenin rapidly induces loss of IESCs and intestinal homeostasis. Conversely, N-terminally recruited co-factors fine-tune β-catenin’s transcriptional output to ensure proper self-renewal and proliferative behaviour of IESCs. Impairment of N-terminal interactions triggers transient hyperproliferation of IESCs, eventually resulting in exhaustion of the self-renewing stem cell pool. IESC mis-differentiation, accompanied by unfolded protein response stress and immune infiltration, results in a process resembling aberrant “villisation” of intestinal crypts. Our data suggest that IESC-specific Wnt/β-catenin output requires selective modulation of gene expression by transcriptional co-factors.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Nature Publishing Group
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Differential regulation of β-catenin-mediated transcription via N- and C-terminal co-factors governs identity of murine intestinal epithelial stem cells
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2021-03-01
ethz.journal.title
Nature Communications
ethz.journal.volume
12
en_US
ethz.journal.issue
1
en_US
ethz.journal.abbreviated
Nat Commun
ethz.pages.start
1368
en_US
ethz.size
16 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
London
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02060 - Dep. Biosysteme / Dep. of Biosystems Science and Eng.::09711 - Moor, Andreas / Moor, Andreas
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02060 - Dep. Biosysteme / Dep. of Biosystems Science and Eng.::09711 - Moor, Andreas / Moor, Andreas
ethz.date.deposited
2021-03-14T05:26:35Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2021-03-16T21:41:38Z
ethz.rosetta.lastUpdated
2022-03-29T05:49:04Z
ethz.rosetta.versionExported
true
ethz.COinS
ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.atitle=Differential%20regulation%20of%20%CE%B2-catenin-mediated%20transcription%20via%20N-%C2%A0and%20C-terminal%20co-factors%20governs%20identity%20of%20murine%20intestinal%20&rft.jtitle=Nature%20Communications&rft.date=2021&rft.volume=12&rft.issue=1&rft.spage=1368&rft.issn=2041-1723&rft.au=Borrelli,%20Costanza&Valenta,%20Tomas&Handler,%20Kristina&V%C3%A9lez,%20Karelia&Gurtner,%20Alessandra&rft.genre=article&rft_id=info:doi/10.1038/s41467-021-21591-9&
 Search print copy at ETH Library

Files in this item

Thumbnail

Publication type

Show simple item record