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| Status |
Public on Jul 03, 2024 |
| Title |
Chromatin Remodeling Drives Immune-Fibroblast Cell Communication in Heart Failure (scATAC-Seq) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Chronic inflammation and tissue fibrosis are common stress responses that worsen organ function, yet their crosstalk is poorly understood. Here, we show that conditional deletion of the transcription co-activator Brd4 in Cx3cr1-positive myeloid cells ameliorates heart failure and is associated with a dramatic reduction in fibroblast activation. We identified a specific BRD4-occupied enhancer in Cx3cr1-positive cells that controls expression of Interleukin-1 beta (Il1b), and show that secreted IL1B activates a p65/RELA-dependent enhancer downstream of MEOX1, driving a profibrotic response in human cardiac fibroblasts. In vivo, antibody-mediated IL1B neutralization prevented stress-induced expression of MEOX1, inhibited fibroblast activation, and improved cardiac function in heart failure. The elucidation of BRD4-dependent crosstalk between a specific immune cell subset and fibroblasts through IL1B provides new therapeutic strategies for heart disease and other disorders of chronic inflammation and maladaptive tissue remodeling.
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| Overall design |
Single cell or nuclei RNAseq from adult heart in the context of BET bromodomain inhibition, BRD4 genetic deletion and neutralization of the cytokine IL1B
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| Contributor(s) |
Alexanian M, Pelonero A, Przytycki PF, Nishino T |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Dec 23, 2022 |
| Last update date |
Jul 03, 2024 |
| Contact name |
Michael Alexanian |
| Organization name |
Gladstone Institutes
|
| Street address |
1650 Owens Street
|
| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94158 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (9)
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| This SubSeries is part of SuperSeries: |
| GSE221699 |
Chromatin Remodeling Drives Immune-Fibroblast Cell Communication in Heart Failure |
|
| Relations |
| BioProject |
PRJNA915388 |
| SRA |
SRP414684 |
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