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Crypt density and recruited enhancers underlie intestinal tumour initiation

ABSTRACT: Crypt density and recruited enhancers underlie intestinal tumour initiation

PROVIDER: PRJNA1007859 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25722165.fastq.gz	Fastqsanger.gz
	SRR25722166.fastq.gz	Fastqsanger.gz
	SRR25722167.fastq.gz	Fastqsanger.gz
	SRR25722168_1.fastq.gz	Fastqsanger.gz
	SRR25722168_2.fastq.gz	Fastqsanger.gz

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Crypt density and recruited enhancers underlie intestinal tumour initiation

Project description:Oncogenic mutations that drive colorectal cancer can be present in healthy intestines for long periods without overt consequence. Mutation of Adenomatous polyposis coli (Apc), the most common initiating event in conventional adenomas, activates Wnt signaling, hence conferring fitness on mutant intestinal stem cells (ISCs). Apc mutations may occur in ISCs that arose by routine self-renewal or by dedifferentiation of their progeny. Although ISCs of these different origins are fundamentally similar, it is unclear if both generate tumours equally well in uninjured intestines. Also unknown is whether cis-regulatory elements are substantively modulated upon Wnt hyperactivation or as a feature of subsequent tumours. Here, we show in two mouse models that adenomas are not an obligatory outcome of Apc deletion in either ISC source but require proximity of mutant intestinal crypts. Reduced crypt density abrogates, and aggregation of mutant colonic crypts augments, adenoma formation. Moreover, adenoma-resident ISCs open chromatin at thousands of enhancers that are inaccessible in Apc-null ISCs not associated with adenomas. These cis-elements explain adenoma-selective gene activity and persist, with little further expansion of the repertoire, as other oncogenic mutations accumulate. Thus, cooperativity between neighbouring mutant crypts and new accessibility at specific enhancers are key steps early in intestinal tumourigenesis.

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Crypt density and recruited enhancers underlie intestinal tumour initiation

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Crypt density and recruited enhancers underlie intestinal tumour initiation

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

2024-11-15 | GSE241384 | GEO

Expression data from mouse crypt

Project description:Paneth cells originate in the stem cell region near the bottom of the gland and release a large number of secretory granules containing antimicrobials. The antimicrobial-rich granules are discharged into the crypt lumen and prevent microbial invasion of the crypt and defend the gland stem cells from microbial damage. We examined the global gene expression profiles in crypt IECs using the Clariom S sDNA array. We analyzed mRNA panels of antimicrobial peptides (AMPs) produced in CSN8ΔIEC and CSN8fl/fl mice.

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