Notch signaling drives development of Barrett’s metaplasia from Dclk1-positive epithelial tuft cells in the murine gastric mucosa
Abstract: Barrett’s esophagus (BE) is a precursor to esophageal adenocarcinoma (EAC), but its cellular origin and mechanism of neoplastic progression remain unresolved. Notch signaling, which plays a key role in regulating intestinal stem cell maintenance, has been implicated in a number of cancers. The kinase Dclk1 labels epithelial post-mitotic tuft cells at the squamo-columnar junction (SCJ), and has also been proposed to contribute to epithelial tumor growth. Here, we find that genetic activation of intracellular Notch signaling in epithelial Dclk1-positive tuft cells resulted in the accelerated development of metaplasia and dysplasia in a mouse model of BE (pL2.Dclk1.N2IC mice). In contrast, genetic ablation of Notch receptor 2 in Dclk1-positive cells delayed BE progression (pL2.Dclk1.N2fl mice), and led to increased secretory cell differentiation. The accelerated BE progression in pL2.Dclk1.N2IC mice correlated with changes to the transcriptomic landscape, most notably for the activation of oncogenic, proliferative pathways in BE tissues, in contrast to upregulated Wnt signalling in pL2.Dclk1.N2fl mice. Collectively, our data show that Notch activation in Dclk1-positive tuft cells in the gastric cardia can contribute to BE development
- Standort
-
Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
-
Online-Ressource
- Sprache
-
Englisch
- Anmerkungen
-
Scientific reports. - 11, 1 (2021) , 4509, ISSN: 2045-2322
- Ereignis
-
Veröffentlichung
- (wo)
-
Freiburg
- (wer)
-
Universität
- (wann)
-
2021
- Urheber
-
Kunze, Bettina
Middelhoff, Moritz
Maurer, H. Carlo
Agibalova, Tatiana
Anand, Akanksha
Bührer, Anne-Marie
Fang, Hsin-Yu
Baumeister, Theresa
Steiger, Katja
Strangmann, Julia
Schmid, Roland M.
Wang, Timothy C.
Quante, Michael
- DOI
-
10.1038/s41598-021-84011-4
- URN
-
urn:nbn:de:bsz:25-freidok-1936633
- Rechteinformation
-
Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
-
15.08.2025, 07:27 MESZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Kunze, Bettina
- Middelhoff, Moritz
- Maurer, H. Carlo
- Agibalova, Tatiana
- Anand, Akanksha
- Bührer, Anne-Marie
- Fang, Hsin-Yu
- Baumeister, Theresa
- Steiger, Katja
- Strangmann, Julia
- Schmid, Roland M.
- Wang, Timothy C.
- Quante, Michael
- Universität
Entstanden
- 2021
Ähnliche Objekte (12)
Potential role of the microbiome in Barrett's esophagus and esophageal adenocarcinoma
![Molecular mechanisms of gastrointestinal carcinogenesis in gastric and espohageal [esophageal] cancer](/assets/placeholder/searchResultMediaNoDigitisedMedia.png)
Molecular mechanisms of gastrointestinal carcinogenesis in gastric and espohageal [esophageal] cancer
Differenzielle transkriptionelle Regulation der humanen Telomerase in einem zellulären Karzinogenese-Modell am Beispiel des Plattenepithelkarzinoms des Ösophagus
The role of inflammation and the intestinal microbiome in a mouse model of Barrett esophagus
A Dietary-Shaped Gut Microbiome Accelerates Progression From Barrett´s Esophagus To Adenocarcinoma via Systemic Bile Acids
Targeting c-MET for endoscopic detection of dysplastic lesions within Barrett’s esophagus using EMI-137 fluorescence imaging
Menschenwürde und personale Autonomie : demokratische Werte im Kontext der Lebenswissenschaften
Einführung in die allgemeine Ethik
Personale Identität
Dignidade humana e autonomia pessoal : valores democráticos no contexto das ciências da vida
Personales Leben und menschlicher Tod : personale Identität als Prinzip der biomedizinischen Ethik
Einführung in die allgemeine Ethik
Potential role of the microbiome in Barrett's esophagus and esophageal adenocarcinoma
Molecular mechanisms of gastrointestinal carcinogenesis in gastric and espohageal [esophageal] cancer
Differenzielle transkriptionelle Regulation der humanen Telomerase in einem zellulären Karzinogenese-Modell am Beispiel des Plattenepithelkarzinoms des Ösophagus
The role of inflammation and the intestinal microbiome in a mouse model of Barrett esophagus
A Dietary-Shaped Gut Microbiome Accelerates Progression From Barrett´s Esophagus To Adenocarcinoma via Systemic Bile Acids
Targeting c-MET for endoscopic detection of dysplastic lesions within Barrett’s esophagus using EMI-137 fluorescence imaging
Menschenwürde und personale Autonomie : demokratische Werte im Kontext der Lebenswissenschaften
Einführung in die allgemeine Ethik
Personale Identität
Dignidade humana e autonomia pessoal : valores democráticos no contexto das ciências da vida
Personales Leben und menschlicher Tod : personale Identität als Prinzip der biomedizinischen Ethik
Einführung in die allgemeine Ethik
Potential role of the microbiome in Barrett's esophagus and esophageal adenocarcinoma
Molecular mechanisms of gastrointestinal carcinogenesis in gastric and espohageal [esophageal] cancer
Differenzielle transkriptionelle Regulation der humanen Telomerase in einem zellulären Karzinogenese-Modell am Beispiel des Plattenepithelkarzinoms des Ösophagus
The role of inflammation and the intestinal microbiome in a mouse model of Barrett esophagus
A Dietary-Shaped Gut Microbiome Accelerates Progression From Barrett´s Esophagus To Adenocarcinoma via Systemic Bile Acids
Targeting c-MET for endoscopic detection of dysplastic lesions within Barrett’s esophagus using EMI-137 fluorescence imaging
Menschenwürde und personale Autonomie : demokratische Werte im Kontext der Lebenswissenschaften
Einführung in die allgemeine Ethik
Personale Identität
Dignidade humana e autonomia pessoal : valores democráticos no contexto das ciências da vida
Personales Leben und menschlicher Tod : personale Identität als Prinzip der biomedizinischen Ethik