000293861 001__ 293861
000293861 005__ 20250126014848.0
000293861 0247_ $$2doi$$a10.1136/gutjnl-2024-332095
000293861 0247_ $$2pmid$$apmid:39353725
000293861 0247_ $$2ISSN$$a0017-5749
000293861 0247_ $$2ISSN$$a1468-3288
000293861 0247_ $$2altmetric$$aaltmetric:172857548
000293861 037__ $$aDKFZ-2024-01991
000293861 041__ $$aEnglish
000293861 082__ $$a610
000293861 1001_ $$aLian, Guodong$$b0
000293861 245__ $$ap53 mutation biases squamocolumnar junction progenitor cells towards dysplasia rather than metaplasia in Barrett's oesophagus.
000293861 260__ $$aLondon$$bBMJ Publishing Group$$c2025
000293861 3367_ $$2DRIVER$$aarticle
000293861 3367_ $$2DataCite$$aOutput Types/Journal article
000293861 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1737369295_3882
000293861 3367_ $$2BibTeX$$aARTICLE
000293861 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000293861 3367_ $$00$$2EndNote$$aJournal Article
000293861 500__ $$a2025 Jan 17;74(2):182-196
000293861 520__ $$aWhile p53 mutations occur early in Barrett's oesophagus (BE) progression to oesophageal adenocarcinoma (EAC), their role in gastric cardia stem cells remains unclear.This study investigates the impact of p53 mutation on the fate and function of cardia progenitor cells in BE to EAC progression, particularly under the duress of chronic injury.We used a BE mouse model (L2-IL1β) harbouring a Trp53 mutation (R172H) to study the effects of p53 on Cck2r+ cardia progenitor cells. We employed lineage tracing, pathological analysis, organoid cultures, single-cell RNA sequencing (scRNA-seq) and computational analyses to investigate changes in progenitor cell behaviour, differentiation patterns and tumour progression. Additionally, we performed orthotopic transplantation of sorted metaplastic and mutant progenitor cells to assess their tumourigenic potential in vivo.The p53 mutation acts as a switch to expand progenitor cells and inhibit their differentiation towards metaplasia, but only amidst chronic injury. In L2-IL1β mice, p53 mutation increased progenitors expansion and lineage-tracing with a shift from metaplasia to dysplasia. scRNA-seq revealed dysplastic cells arise directly from mutant progenitors rather than progressing through metaplasia. In vitro, p53 mutation enhanced BE progenitors' organoid-forming efficiency, growth, DNA damage resistance and progression to aneuploidy. Sorted metaplastic cells grew poorly with no progression to dysplasia, while mutant progenitors gave rise to dysplasia in orthotopic transplantation. Computational analyses indicated that p53 mutation inhibited stem cell differentiation through Notch activation.p53 mutation contributes to BE progression by increasing expansion and fitness of undifferentiated cardia progenitors and preventing their differentiation towards metaplasia.
000293861 536__ $$0G:(DE-HGF)POF4-313$$a313 - Krebsrisikofaktoren und Prävention (POF4-313)$$cPOF4-313$$fPOF IV$$x0
000293861 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de
000293861 650_7 $$2Other$$aBARRETT'S METAPLASIA
000293861 650_7 $$2Other$$aBARRETT'S OESOPHAGUS
000293861 650_7 $$2Other$$aDYSPLASIA
000293861 650_7 $$2Other$$aOESOPHAGEAL CANCER
000293861 650_7 $$2Other$$aSTEM CELLS
000293861 7001_ $$aMalagola, Ermanno$$b1
000293861 7001_ $$aWei, Chengguo$$b2
000293861 7001_ $$aShi, Qiongyu$$b3
000293861 7001_ $$aZhao, Junfei$$b4
000293861 7001_ $$aHata, Masahiro$$b5
000293861 7001_ $$00000-0002-1717-4870$$aKobayashi, Hiroki$$b6
000293861 7001_ $$aOchiai, Yosuke$$b7
000293861 7001_ $$aZheng, Biyun$$b8
000293861 7001_ $$aZhi, Xiaofei$$b9
000293861 7001_ $$aWu, Feijing$$b10
000293861 7001_ $$aTu, Ruhong$$b11
000293861 7001_ $$aNápoles, Osmel Companioni$$b12
000293861 7001_ $$aSu, Wenjing$$b13
000293861 7001_ $$aLi, Leping$$b14
000293861 7001_ $$aJing, Changqing$$b15
000293861 7001_ $$aChen, Man$$b16
000293861 7001_ $$aZamechek, Leah$$b17
000293861 7001_ $$aFriedman, Richard$$b18
000293861 7001_ $$0P:(DE-He78)5eecfbb3a55c32d69c08f67104c5c62b$$aNowicki-Osuch, Karol$$b19$$udkfz
000293861 7001_ $$00000-0002-8497-582X$$aQuante, Michael$$b20
000293861 7001_ $$aQue, Jianwen$$b21
000293861 7001_ $$00000-0002-7940-8310$$aWang, Timothy C$$b22
000293861 773__ $$0PERI:(DE-600)1492637-4$$a10.1136/gutjnl-2024-332095$$gp. gutjnl-2024-332095 -$$n2$$p182-196$$tGut$$v74$$x0017-5749$$y2025
000293861 909CO $$ooai:inrepo02.dkfz.de:293861$$pVDB
000293861 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)5eecfbb3a55c32d69c08f67104c5c62b$$aDeutsches Krebsforschungszentrum$$b19$$kDKFZ
000293861 9131_ $$0G:(DE-HGF)POF4-313$$1G:(DE-HGF)POF4-310$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vKrebsrisikofaktoren und Prävention$$x0
000293861 9141_ $$y2024
000293861 915__ $$0StatID:(DE-HGF)0430$$2StatID$$aNational-Konsortium$$d2023-10-21$$wger
000293861 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bGUT : 2022$$d2023-10-21
000293861 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2023-10-21
000293861 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2023-10-21
000293861 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central$$d2023-10-21
000293861 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2023-10-21
000293861 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2023-10-21
000293861 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2023-10-21
000293861 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2023-10-21
000293861 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2023-10-21
000293861 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2023-10-21
000293861 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2023-10-21
000293861 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2023-10-21
000293861 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2023-10-21
000293861 915__ $$0StatID:(DE-HGF)1110$$2StatID$$aDBCoverage$$bCurrent Contents - Clinical Medicine$$d2023-10-21
000293861 915__ $$0StatID:(DE-HGF)9920$$2StatID$$aIF >= 20$$bGUT : 2022$$d2023-10-21
000293861 9201_ $$0I:(DE-He78)C150-20160331$$kC150$$lNWG Tumorgenese und molekulare Krebsprävention$$x0
000293861 980__ $$ajournal
000293861 980__ $$aVDB
000293861 980__ $$aI:(DE-He78)C150-20160331
000293861 980__ $$aUNRESTRICTED