Intestinal Paneth cell differentiation relies on asymmetric regulation of Wnt signaling by Daam1/2

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F23%3A00583497" target="_blank" >RIV/68081707:_____/23:00583497 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14310/23:00132483

Výsledek na webu

<a href="https://www.science.org/doi/10.1126/sciadv.adh9673" target="_blank" >https://www.science.org/doi/10.1126/sciadv.adh9673</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1126/sciadv.adh9673" target="_blank" >10.1126/sciadv.adh9673</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Intestinal Paneth cell differentiation relies on asymmetric regulation of Wnt signaling by Daam1/2

Popis výsledku v původním jazyce

The mammalian intestine is one of the most rapidly self-renewing tissues, driven by stem cells residing at the crypt bottom. Paneth cells form a major element of the niche microenvironment providing various growth factors to orchestrate intestinal stem cell homeostasis, such as Wnt3. Different Wnt ligands can selectively activate beta-catenin-dependent (canonical) orindependent (noncanonical) signaling. Here, we report that the Dishevelled-associated activator of morphogenesis 1 (Daam1) and its paralogue Daam2 asymmetrically regulate canonical and noncanonical Wnt (Wnt/PCP) signaling. Daam1/2 interacts with the Wnt inhibitor RNF43, and Daam1/2 double knockout stimulates canonical Wnt signaling by preventing RNF43-dependent degradation of the Wnt receptor, Frizzled (Fzd). Single-cell RNA sequencing analysis revealed that Paneth cell differentiation is impaired by Daam1/2 depletion because of defective Wnt/PCP signaling. Together, we identified Daam1/2 as an unexpected hub molecule coordinating both canonical and noncanonical Wnt, which is fundamental for specifying an adequate number of Paneth cells.

Název v anglickém jazyce

Intestinal Paneth cell differentiation relies on asymmetric regulation of Wnt signaling by Daam1/2

Popis výsledku anglicky

The mammalian intestine is one of the most rapidly self-renewing tissues, driven by stem cells residing at the crypt bottom. Paneth cells form a major element of the niche microenvironment providing various growth factors to orchestrate intestinal stem cell homeostasis, such as Wnt3. Different Wnt ligands can selectively activate beta-catenin-dependent (canonical) orindependent (noncanonical) signaling. Here, we report that the Dishevelled-associated activator of morphogenesis 1 (Daam1) and its paralogue Daam2 asymmetrically regulate canonical and noncanonical Wnt (Wnt/PCP) signaling. Daam1/2 interacts with the Wnt inhibitor RNF43, and Daam1/2 double knockout stimulates canonical Wnt signaling by preventing RNF43-dependent degradation of the Wnt receptor, Frizzled (Fzd). Single-cell RNA sequencing analysis revealed that Paneth cell differentiation is impaired by Daam1/2 depletion because of defective Wnt/PCP signaling. Together, we identified Daam1/2 as an unexpected hub molecule coordinating both canonical and noncanonical Wnt, which is fundamental for specifying an adequate number of Paneth cells.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

10609 - Biochemical research methods

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Science Advances

ISSN

2375-2548

e-ISSN

2375-2548

Svazek periodika

9

Číslo periodika v rámci svazku

47

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

18

Strana od-do

eadh9673

Kód UT WoS článku

001139850400006

EID výsledku v databázi Scopus

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