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| Status |
Public on Sep 10, 2021 |
| Title |
Epigenetic reprogramming of airway macrophages drives polarization and inflammation in muco-obstructive lung disease (ATAC_Treat) |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Lung diseases, such as cystic fibrosis and COPD, are characterized by mucus obstruction and chronic airway inflammation, but their mechanistic link remains poorly understood. Here, we focused on the role of the mucostatic airway microenvironment on epigenetic reprogramming of airway macrophages (AM) and resulting transcriptomic and phenotypical changes. Using a muco-obstructive mouse model (Scnn1b-transgenic), we identified epigenetically controlled, differentially regulated pathways and transcription factors involved in inflammatory responses and macrophage polarization. Ex vivo stimulation of wild-type AMs with mucus induced gene expression changes, comparable with those observed in AMs from Scnn1b-transgenic mice. Functionally, AMs from Scnn1b-transgenic mice displayed impaired efferocytosis, phagocytosis and excessive inflammatory responses upon lipopolysaccharide challenge, mediated through enhanced Irf1 activity and expression. Our data show that mucostasis induces epigenetic reprogramming of AMs, leading to changes favoring tissue damage and disease progression. Targeting of these altered AMs may support therapeutic approaches in patients with muco-obstructive lung diseases.
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| Overall design |
RNAseq, ATACseq and tWGBS was performed on wildtype as well as transgene airway macrophages. In addition RNAseq as well as ATACseq was performed on wildtype and transgene airway macrophages upon stimulation with medium or lipopolysaccharide for 12 hours.
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| Contributor(s) |
Hey J, Paulsen M |
| Citation(s) |
34764283 |
| |
| Submission date |
Jul 21, 2020 |
| Last update date |
Nov 30, 2021 |
| Contact name |
Joschka Hey |
| E-mail(s) |
[email protected]
|
| Organization name |
DKFZ
|
| Department |
Cancer epigenomics
|
| Lab |
Plass lab
|
| Street address |
Im Neuenheimer Feld 280
|
| City |
Heidelberg |
| State/province |
Deutschland |
| ZIP/Postal code |
69120 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE154808 |
Epigenetic reprogramming of airway macrophages drives polarization and inflammation in muco-obstructive lung disease |
|
| Relations |
| BioProject |
PRJNA647561 |
| SRA |
SRP272855 |
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