{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE293nnn/GSE293170/"]},"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=GSE293170"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Extracellular stiffness regulates site-specific lung development [AWO]","description":"Extracellular matrix (ECM) stiffness plays a crucial role in regulating cell fate and maturation, but its influence on lung development is limited known. Here we utilized stiffness-tunable gelatin methacryloyl (GelMA) hydrogels to investigate how ECM stiffness influences site-specific lung development in a stem cell-derived lung organoid model. We found increased stiffness promoted NKX2-1+ lung progenitor cells (LPCs) generation. In airway organoids (hAWOs), stiff hydrogels directed proximal airway differentiation enriched with goblet, ciliated, and basal cells; whereas the decreased stiffness favored emergence of secretory cells in the proximal-distal transition zone and distal airway. In alveolar organoids (hALOs), increased stiffness enhanced AT2 and AT1 cells transition. Moreover, infection assays with Omicron BA.1.1 and Delta variants recapitulated the proximal-to-distal tropism of SARS-CoV-2 in the lung. Transcriptomic sequencing revealed ECM stiffness regulates lung development via Hippo, TGF-β, HIF and Wnt pathways. These findings advance mechanism understanding of ECM stiffness on lung development and provide a novel mechanical regulation for generating site-specific lung organoids.","dates":{"publication":"2026/06/02"},"accession":"GSE293170","cross_references":{"GSM":["GSM8877764","GSM8877765","GSM8877763"],"GPL":["34284"],"GSE":["293170"],"taxon":["Homo sapiens"]}}