{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE339nnn/GSE339221/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE339221"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"V-ATPase-Driven Lysosomal Activation Orchestrates MEK2-Induced Endothelial Reprogramming","description":"Direct lineage reprogramming holds therapeutic promise but often depends on transcription factor overexpression, resulting in unstable phenotypes. Here, we use RNA-sequencing to characterize a novel strategy converting fibroblasts into endothelial-like cells through activation of lysosomal activity. Constitutively active MEK2 induces a transcriptional endothelial gene program via sustained MAPK/ERK signaling, leading to enhanced vacuolar ATPase (V-ATPase) activity, lysosomal acidification, extracellular matrix degradation, and angiogenic behavior. Transcriptomic profiling reveals that V-ATPase inhibition impairs induction of endothelial gene expression, whereas pharmacologic V-ATPase activation with EN6 recapitulates key transcriptional features of reprogramming and promotes nuclear translocation of TFEB, a master lysosomal regulator. Consistently, TFEB overexpression, particularly a phospho-deficient mutant, boosts lysosomal gene expression and enhances the endothelial transcriptional signature. This dataset defines a MAPK–V-ATPase–TFEB axis driving endothelial reprogramming at the transcriptional level and provides a resource for exploring the lysosome as a central hub for cell fate transitions","dates":{"publication":"2026/09/03"},"accession":"GSE339221","cross_references":{"GSM":["GSM9890521","GSM9890520","GSM9890523","GSM9890522","GSM9890530","GSM9890529","GSM9890518","GSM9890517","GSM9890528","GSM9890519","GSM9890525","GSM9890524","GSM9890516","GSM9890527","GSM9890526"],"GPL":["34290"],"GSE":["339221"],"taxon":["Mus musculus"]}}