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HOXA13 in etiology and oncogenic potential of Barrett’s esophagus [BAR-T]

ABSTRACT: HOXA13 in etiology and oncogenic potential of Barrett’s esophagus [BAR-T]

PROVIDER: PRJNA724027 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14308643.fastq.gz	Fastqsanger.gz
	SRR14308644.fastq.gz	Fastqsanger.gz
	SRR14308645.fastq.gz	Fastqsanger.gz
	SRR14308646.fastq.gz	Fastqsanger.gz
	SRR14308647.fastq.gz	Fastqsanger.gz

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HOXA13 in etiology and oncogenic potential of Barrett’s esophagus [BAR-T]

Project description:Barrett’s esophagus in gastrointestinal reflux patients constitutes a columnar epithelium with distal characteristics, prone to progress to esophageal adenocarcinoma. HOX genes are known mediators of position-dependent morphology. Here we show HOX collinearity in the adult gut while Barrett’s esophagus shows high HOXA13 expression in stem cells and their progeny. HOXA13 overexpression appears sufficient to explain both the phenotype (through downregulation of the epidermal differentiation complex) and the oncogenic potential of Barrett’s esophagus. Intriguingly, employing a mouse model that contains a reporter coupled to the HOXA13 promotor we identify single HOXA13-positive cells distally from the physiological esophagus, which is mirrored in human physiology, but increased in BE. Additionally, we observe that HOXA13 expression confers a competitive advantage to cells. We thus propose that Barrett’s esophagus and associated esophageal adenocarcinoma is the consequence of expansion of this gastro-esophageal HOXA13-expressing compartment following epithelial injury.

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HOXA13 in etiology and oncogenic potential of Barrett’s esophagus [EPC2]

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HOXA13 in etiology and oncogenic potential of Barrett’s esophagus [KH2 mESC diff]

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HOXA13 in etiology and oncogenic potential of Barrett’s esophagus [KH2 mESC non diff]

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HOXA13 in etiology and oncogenic potential of Barrett’s esophagus

Project description:HOXA13 in etiology and oncogenic potential of Barrett’s esophagus

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HOXA13 in etiology and oncogenic potential of Barrett’s esophagus [EPC2]

Project description:HOXA13 in etiology and oncogenic potential of Barrett’s esophagus [EPC2]

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HOXA13 in etiology and oncogenic potential of Barrett’s esophagus [KH2 mESC diff]

Project description:HOXA13 in etiology and oncogenic potential of Barrett’s esophagus [KH2 mESC diff]

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HOXA13 in etiology and oncogenic potential of Barrett’s esophagus [KH2 mESC non diff]

Project description:HOXA13 in etiology and oncogenic potential of Barrett’s esophagus [KH2 mESC non diff]

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Cloning Barrett’s esophagus stem cells

Project description:Barrett’s esophagus is a precancerous lesion that confers a significant risk of esophageal adenocarcinoma. Strategies for selective eradication of Barrett’s have been stymied by our inability to identify the Barrett’s stem cell. Here we employ novel technologies to clone patient-matched stem cells of Barrett’s, gastric, and esophageal epithelium. Genomic analyses of Barrett’s stem cells reveal a patient-specific mutational spectrum ranging from low somatic variation similar to patient-matched gastric epithelial stem cells to ones marked by extensive heterozygous alteration of genes implicated in tumor suppression, epithelial planarity, and epigenetic regulation. Transplantation of transformed Barrett’s stem cells yields tumors with hallmarks of esophageal adenocarcinoma, whereas transformed esophageal stem cells yield squamous cell carcinomas. Thus Barrett’s develops from cells distinct from local eponymous epithelia, emerges without obvious driver mutations, and likely progresses through and from the generation of dominant clones. These findings define a stem cell target for preemptive therapies of a precancerous lesion.

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HOXA13 in etiology and oncogenic potential of Barrett’s esophagus

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-04-24 | GSE173170 | GEO