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Hedgehog signaling alters the balance of fibroblast subtypes in pancreatic cancer [bulk RNA-seq]

ABSTRACT: Hedgehog signaling alters the balance of fibroblast subtypes in pancreatic cancer [bulk RNA-seq]

PROVIDER: PRJNA659374 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12515587_1.fastq.gz	Fastqsanger.gz
	SRR12515587_2.fastq.gz	Fastqsanger.gz
	SRR12515588_1.fastq.gz	Fastqsanger.gz
	SRR12515588_2.fastq.gz	Fastqsanger.gz
	SRR12515589_1.fastq.gz	Fastqsanger.gz

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Hedgehog signaling alters the balance of fibroblast subtypes in pancreatic cancer

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Hedgehog signaling alters the balance of fibroblast subtypes in pancreatic cancer [scRNA-seq]

Project description:A better understanding of the roles of signaling pathways differentially activated in distinct fibroblast populations will shed light on the complexity of fibroblast heterogeneity in pancreatic cancer. Here, we show that Hedgehog pathway inhibition alters the fibroblast composition towards a more inflammatory microenvironment, opening the possibility for future combination therapies.

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Hedgehog signaling alters the balance of fibroblast subtypes in pancreatic cancer [bulk RNA-seq]

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Hedgehog signaling alters the balance of fibroblast subtypes in pancreatic cancer

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Inhibition of Hedgehog Signaling Alters Fibroblast Composition in Pancreatic Cancer.

Project description:PurposePancreatic ductal adenocarcinoma (PDAC) is a deadly disease characterized by an extensive fibroinflammatory stroma, which includes abundant cancer-associated fibroblast (CAF) populations. PDAC CAFs are heterogeneous, but the nature of this heterogeneity is incompletely understood. The Hedgehog pathway functions in PDAC in a paracrine manner, with ligands secreted by cancer cells signaling to stromal cells in the microenvironment. Previous reports investigating the role of Hedgehog signaling in PDAC have been contradictory, with Hedgehog signaling alternately proposed to promote or restrict tumor growth. In light of the newly discovered CAF heterogeneity, we investigated how Hedgehog pathway inhibition reprograms the PDAC microenvironment.Experimental designWe used a combination of pharmacologic inhibition, gain- and loss-of-function genetic experiments, cytometry by time-of-flight, and single-cell RNA sequencing to study the roles of Hedgehog signaling in PDAC.ResultsWe found that Hedgehog signaling is uniquely activated in fibroblasts and differentially elevated in myofibroblastic CAFs (myCAF) compared with inflammatory CAFs (iCAF). Sonic Hedgehog overexpression promotes tumor growth, while Hedgehog pathway inhibition with the smoothened antagonist, LDE225, impairs tumor growth. Furthermore, Hedgehog pathway inhibition reduces myCAF numbers and increases iCAF numbers, which correlates with a decrease in cytotoxic T cells and an expansion in regulatory T cells, consistent with increased immunosuppression.ConclusionsHedgehog pathway inhibition alters fibroblast composition and immune infiltration in the pancreatic cancer microenvironment.

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Liquid Application Dosing Alters the Physiology of Air-Liquid Interface Primary Bronchial Epithelial Cell/Lung Fibroblast Co-Cultures and In Vitro Testing Relevant Endpoints

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2023-09-19 | GSE228283 | GEO

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