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| 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
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| 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.
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| Overall design |
Comparative chromatin opening profiling analysis of ATAC-seq data for basal stem cells from CDH patients and term and preterm controls.
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| Contributor(s) |
Wagner R, Amonkar GM, Wang W, Lerou PH, Ai X |
| Citation(s) |
36731066 |
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| Submission date |
Aug 22, 2022 |
| Last update date |
Aug 02, 2023 |
| Contact name |
Xingbin Ai |
| E-mail(s) |
xai@mgh.harvard.edu
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| Organization name |
MASSACHUSETTS GENERAL HOSPITAL
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| Department |
Pediatrics
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| Street address |
55 Fruit St
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02114 |
| Country |
USA |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (8)
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| GSM6502200 |
ATAC-Seq BSC, Ctrl, rep2 |
| GSM6502201 |
ATAC-Seq BSC, Ctrl, rep3 |
| GSM6502202 |
ATAC-Seq BSC, Ctrl, rep4 |
| GSM6502203 |
ATAC-Seq BSC, Ctrl, rep5 |
| GSM6502204 |
ATAC-Seq BSC, Ctrl, rep6 |
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| This SubSeries is part of SuperSeries: |
| GSE211790 |
A tracheal aspirate-derived airway basal cell model reveals a proinflammatory epithelial defect in congenital diaphragmatic hernia |
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| Relations |
| BioProject |
PRJNA872127 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE211788_RAW.tar |
728.6 Mb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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