{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE335nnn/GSE335271/"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE335271"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Matrix viscoelasticity promotes cardiac fibroblast-macrophage fibrotic crosstalk","description":"Cardiac fibrosis is driven by dynamic crosstalk between cardiac fibroblasts and macrophages, yet how tissue mechanics regulate these interactions remains poorly defined. Here, we introduce a novel viscoelastic coculture platform that enables precise interrogation of mechanical and paracrine signaling in a physiologically relevant context. Counterintuitively, we found that soft, viscous environments promote human induced pluripotent stem cell-derived cardiac fibroblast activation and macrophage healing phenotypes, while stiff environments bias macrophages toward inflammation. Coculture in soft, viscous matrices amplifies reciprocal pro-fibrotic signaling, and sequential exposure to inflammatory followed by healing activated macrophages, which recapitulate in vivo dynamics, further exacerbates fibroblast activation. Mechanistically, we identified a viscoelasticity-driven positive feedback loop involving inflammatory cytokines IL6, CCL5, and CCL2 as well as healing cytokines VEGFA and CTGF. This work establishes tissue viscoelasticity as a central regulator of immune–stromal interactions and provides a broadly applicable platform for dissecting mechanobiological drivers of fibrosis.","dates":{"publication":"2026/09/02"},"accession":"GSE335271","cross_references":{"GSM":["GSM9809267","GSM9809268","GSM9809265","GSM9809266","GSM9809269","GSM9809270","GSM9809271","GSM9809263","GSM9809264","GSM9809262"],"GPL":["34284"],"GSE":["335271"],"taxon":["Homo sapiens"]}}