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Series GSE211788 Query DataSets for GSE211788
Status Public on Jun 30, 2023
Title A tracheal aspirate-derived airway basal cell model reveals a proinflammatory epithelial defect in congenital diaphragmatic hernia (ATAC-Seq)
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary 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.
Overall design Comparative chromatin opening profiling analysis of ATAC-seq data for basal stem cells from CDH patients and term and preterm controls.
Contributor(s) Wagner R, Amonkar GM, Wang W, Lerou PH, Ai X
Citation(s) 36731066
Submission date Aug 22, 2022
Last update date Aug 02, 2023
Contact name Xingbin Ai
Department Pediatrics
Street address 55 Fruit St
City Boston
State/province MA
ZIP/Postal code 02114
Country USA
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (8)
GSM6502197 ATAC-Seq BSC, CDH, rep1
GSM6502198 ATAC-Seq BSC, CDH, rep2
GSM6502199 ATAC-Seq BSC, Ctrl, rep1
This SubSeries is part of SuperSeries:
GSE211790 A tracheal aspirate-derived airway basal cell model reveals a proinflammatory epithelial defect in congenital diaphragmatic hernia
BioProject PRJNA872127

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Supplementary file Size Download File type/resource
GSE211788_RAW.tar 728.6 Mb (http)(custom) TAR (of BW)
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Raw data are available in SRA
Processed data provided as supplementary file

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