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A tracheal aspirate-derived airway basal cell model reveals a proinflammatory epithelial defect in congenital diaphragmatic hernia (ATAC-Seq)

ABSTRACT: A tracheal aspirate-derived airway basal cell model reveals a proinflammatory epithelial defect in congenital diaphragmatic hernia (ATAC-Seq)

PROVIDER: PRJNA872127 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21226600_1.fastq.gz	Fastqsanger.gz
	SRR21226600_2.fastq.gz	Fastqsanger.gz
	SRR21226601_1.fastq.gz	Fastqsanger.gz
	SRR21226601_2.fastq.gz	Fastqsanger.gz
	SRR21226602_1.fastq.gz	Fastqsanger.gz

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Rabbit Model of Fetal Tracheal Occlusion for Congenital Diaphragmatic Hernia

Project description:Analysis of embronic day 30.5 (E30.5) fetal rabbit left lung after creation of diapragmatic hernia (DH) at E25 and tracheal occlusion (TO) at E27. The fetuses of timed pregnant New Zealand rabbits were subjected to creation of a left diaphragmatic hernia at E25 with or without tracheal occlusion at E27. At E30.5, the fetuses were sacrificed with collection of the lateral aspect of the left upper lobe for NextGen mRNA sequencing.

2016-07-26 | E-GEOD-84811 | biostudies-arrayexpress

A tracheal aspirate-derived airway basal cell model reveals a proinflammatory epithelial defect in congenital diaphragmatic hernia (RNA-Seq)

Project description:Congenital diaphragmatic hernia (CDH) is characterized by incomplete closure of the diaphragm and lung hypoplasia. The pathophysiology of lung defects in CDH is poorly understood. To establish a translational model of human airway epithelium in CDH for pathogenic investigation and therapeutic testing, we developed a robust methodology of epithelial progenitor derivation from tracheal aspirates of newborns. Basal stem cells from CDH patients and preterm and term, non-CDH controls were derived and analyzed by bulk RNA-sequencing, ATAC-sequencing, and air-liquid-interface differentiation. Transcriptomic and epigenetic profiling of CDH and non-CDH basal stem cells reveals a disease-specific, proinflammatory signature independent of severity or hernia size. In addition, CDH basal stem cells exhibit defective epithelial differentiation in vitro that recapitulates epithelial phenotypes found in fetal human CDH lung samples and fetal tracheas of the nitrofen rat model of CDH. Furthermore, steroid treatment normalizes epithelial differentiation phenotypes of human CDH basal stem cells in vitro and in nitrofen rat tracheas in vivo. Our findings have identified an interplay between a proinflammatory signature and BSC differentiation as a potential therapeutic target for airway epithelial defects in CDH.

2023-06-30 | GSE211789 | GEO

A tracheal aspirate-derived airway basal cell model reveals a proinflammatory epithelial defect in congenital diaphragmatic hernia (ATAC-Seq)

2023-06-30 | GSE211788 | GEO

A tracheal aspirate-derived airway basal cell model reveals a proinflammatory epithelial defect in congenital diaphragmatic hernia

Project description:A tracheal aspirate-derived airway basal cell model reveals a proinflammatory epithelial defect in congenital diaphragmatic hernia

| PRJNA872126 | ENA

A tracheal aspirate-derived airway basal cell model reveals a proinflammatory epithelial defect in congenital diaphragmatic hernia (RNA-Seq)

Project description:A tracheal aspirate-derived airway basal cell model reveals a proinflammatory epithelial defect in congenital diaphragmatic hernia (RNA-Seq)

| PRJNA872128 | ENA

Rabbit Model of Fetal Tracheal Occlusion for Congenital Diaphragmatic Hernia

Project description:Analysis of embronic day 30.5 (E30.5) fetal rabbit left lung after creation of diapragmatic hernia (DH) at E25 and tracheal occlusion (TO) at E27.

2016-07-26 | GSE84811 | GEO

Effect of treprostinil on rabbit lungs with congenital diaphragmatic hernia

Project description:To investigate the effect of treprostinil pulmonary development in a rabbit model of congenital diaphragmatic hernia.

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A Tracheal Aspirate-derived Airway Basal Cell Model Reveals a Proinflammatory Epithelial Defect in Congenital Diaphragmatic Hernia.

Project description:Rationale: Congenital diaphragmatic hernia (CDH) is characterized by incomplete closure of the diaphragm and lung hypoplasia. The pathophysiology of lung defects in CDH is poorly understood. Objectives: To establish a translational model of human airway epithelium in CDH for pathogenic investigation and therapeutic testing. Methods: We developed a robust methodology of epithelial progenitor derivation from tracheal aspirates of newborns. Basal stem cells (BSCs) from patients with CDH and preterm and term non-CDH control subjects were derived and analyzed by bulk RNA sequencing, assay for transposase accessible chromatin with sequencing, and air-liquid interface differentiation. Lung sections from fetal human CDH samples and the nitrofen rat model of CDH were subjected to histological assessment of epithelial defects. Therapeutics to restore epithelial differentiation were evaluated in human epithelial cell culture and the nitrofen rat model of CDH. Measurements and Main Results: Transcriptomic and epigenetic profiling of CDH and control BSCs reveals a proinflammatory signature that is manifested by hyperactive nuclear factor kappa B and independent of severity and hernia size. In addition, CDH BSCs exhibit defective epithelial differentiation in vitro that recapitulates epithelial phenotypes found in fetal human CDH lung samples and fetal tracheas of the nitrofen rat model of CDH. Furthermore, blockade of nuclear factor kappa B hyperactivity normalizes epithelial differentiation phenotypes of human CDH BSCs in vitro and in nitrofen rat tracheas in vivo. Conclusions: Our findings have identified an underlying proinflammatory signature and BSC differentiation defects as a potential therapeutic target for airway epithelial defects in CDH.

| S-EPMC10161756 | biostudies-literature

A tracheal aspirate-derived airway basal cell model reveals a proinflammatory epithelial defect in congenital diaphragmatic hernia

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

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The miRNA profiles of amniotic fluid-derived extracellular vesicles of congenital diaphragmatic hernia patients.

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