Ontology highlight
ABSTRACT:
PROVIDER: PRJNA724887 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14320000.fastq.gz | Fastqsanger.gz | |||
| SRR14320001.fastq.gz | Fastqsanger.gz | |||
| SRR14320002.fastq.gz | Fastqsanger.gz | |||
| SRR14320003.fastq.gz | Fastqsanger.gz | |||
| SRR14320004.fastq.gz | Fastqsanger.gz |
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Project description:Extracellular matrix remodeling of cardiac tissue is a key contributor to age-related cardiovascular disease and dysfunction. Such remodeling is multifaceted including changes to biochemical composition, architecture, and mechanics, clouding our understanding of how and which extracellular matrix properties contribute to a dysfunctional state. Here we describe a decellularized extracellular matrix-synthetic hydrogel hybrid that independently presents two distinct matrix properties, ligand presentation and stiffness, to cultured cells in vitro, allowing for the identification of their specific roles in cardiac aging. The hybrid scaffold maintains native matrix composition and organization of young or aged murine cardiac tissue, while its mechanical properties can be independently tuned to mimic young or aged tissue stiffness. Seeding these scaffolds with murine primary cardiac fibroblasts, we identify distinct age- and matrix-dependent mechanisms of cardiac fibroblast activation, matrix remodeling, and senescence. Importantly, we show that ligand presentation of young extracellular matrix can outweigh profibrotic stiffness cues typically present in aged extracellular matrix in maintaining or driving cardiac fibroblast quiescence. Ultimately, these tunable scaffolds can enable the discovery of specific extracellular targets to prevent aging dysfunction and promote rejuvenation.
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