{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE272nnn/GSE272972/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"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=GSE272972"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Critical role for the TGF-β1/mTORC1 signalling axis in defining the transcriptional identity of CTHRC1+ pathologic fibroblasts in idiopathic pulmonary fibrosis","description":"Fibroblasts represent key effector cells responsible for fibrogenesis during wound healing and pathological fibrosis, including idiopathic pulmonary fibrosis (IPF), the most rapidly progressive and fatal fibrotic lung disease. Single-cell RNA sequencing of fibrotic lung tissue has identified a novel population of high collagen-producing fibroblasts not present in non-diseased control lung, characterised by high expression of the marker, collagen triple helix repeat containing 1 (CTHRC1). The cardinal pro-fibrotic mediator TGF-β1 has been widely implicated in promoting fibrogenesis in multiple fibrotic conditions. In addition to the canonical Smad signalling pathway, TGF-β1-induced collagen I production is under critical regulatory control by the mTORC1/4E-BP1 signalling hub. Using pharmacological inhibition (dual ATP-competitive mTOR inhibitors and rapamycin) in combination with gene-editing approaches, we now demonstrate that the role of the mTORC1 axis extends to the regulation of over a third of all TGF-β1 regulated matrisome genes. We further show that the global transcriptome of TGF-β1-stimulated fibroblasts matches that of CTHRC1+ pathological fibroblast population in the IPF lung. In contrast, the TGF-β1 induced transcriptome of fibroblasts in which mTORC1-signalling is disrupted (by RPTOR gene editing using CRISPR-Cas9) does not map to any known fibroblast population. These data define, for the first time, a critical role for both TGF-β1 and the mTORC1 signalling hub in determining the transcriptional identity of CTHRC1+ pathological fibroblasts and provide strong scientific support for targeting mTORC1 as a therapeutic strategy in IPF and potentially other fibrotic conditions associated with dysregulated TGF-β1 profibrotic signalling.","dates":{"publication":"2026/07/21"},"accession":"GSE272972","cross_references":{"GSM":["GSM8415849","GSM8415857","GSM8415846","GSM8415845","GSM8415856","GSM8415848","GSM8415847","GSM8415858","GSM8415842","GSM8415853","GSM8415852","GSM8415841","GSM8415855","GSM8415844","GSM8415854","GSM8415843","GSM8415851","GSM8415850"],"GPL":["18573"],"GSE":["272972"],"taxon":["Homo sapiens"],"PMID":["[42685210]"]}}