Transient ACE Inhibition Suppresses Future Fibrogenic Capacity and Heterogeneity of Cardiac Fibroblast Subpopulations
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ABSTRACT:
PROVIDER: PRJNA655239 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12389100.fastq.gz | Fastqsanger.gz | |||
| SRR12389101.fastq.gz | Fastqsanger.gz | |||
| SRR12389102.fastq.gz | Fastqsanger.gz | |||
| SRR12389103.fastq.gz | Fastqsanger.gz | |||
| SRR12389104.fastq.gz | Fastqsanger.gz |
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Project description:Preservation of cell identity is necessary for homeostasis of most adult tissues. This process is challenged every time a tissue undergoes regeneration after stress or injury. In the lethal Duchenne muscular Dystrophy (DMD), skeletal muscle regenerative capacity declines gradually as fibrosis increases. Using genetically engineered-tracing mice, we demonstrate that in dystrophic muscle, specialized cells of muscular, endothelial and hematopoietic origins gain plasticity towards a fibrogenic fate via a TGFβ-mediated pathway. This results in loss of cellular identity and normal function, with deleterious consequences for regeneration. Furthermore, this fibrogenic process involves acquisition of a mesenchymal progenitor multipotent status, illustrating a link between fibrogenesis and gain of progenitor cell functions. As this plasticity was also observed in DMD patients, we propose that mesenchymal transitions impair regeneration and worsen diseases with a fibrotic component.
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