{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE299nnn/GSE299488/"]},"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=GSE299488"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"LY6D Identifies Persistent Tumor-Initiating Cells Driving Pancreatic Tumorigenesis [RNA-seq]","description":"Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy driven by oncogenic KRAS and inflammation-induced cellular heterogeneity, yet the mechanisms underlying tumor-initiating cells (TICs) emergence and maintenance remain unclear. Our study establishes LY6D as a marker of persistent TICs that orchestrate pancreatic cancer progression across all disease stages. Single-cell RNA sequencing of inflammation-driven PDAC models reveals that LY6D+ TICs specifically originate from KRAS-mutant acinar-to-ductal metaplasia (ADM) lesions under inflammatory conditions, maintaining conserved stemness properties and exhibiting a distinctive oxidative phosphorylation (OXPHOS) dependency throughout tumor evolution. Moreover, genetic ablation of Ly6d in KrasG12D pancreata delays tumorigenesis, while forced Ly6d expression enhances tumorigenic potential and metastatic capability. Mechanistically, LY6D-despite lacking intracellular domains-scaffolds lipid raft-associated kinase networks and FOSL1-dependent epigenetic reprogramming to establish a stable pro-tumorigenic state. Clinically, LY6D+ cells are enriched in human PDAC and exhibit conserved stemness and epithelial-mesenchymal transition (EMT) properties. Strikingly, LY6D expression levels demonstrate PDAC-restricted prognostic power. Our work defines LY6D as pan-stage TICs marker linking cellular plasticity to PDAC initiation and progression, offering new avenues for early detection and interception of this lethal malignancy.","dates":{"publication":"2026/04/09"},"accession":"GSE299488","cross_references":{"GSM":["GSM9039727","GSM9039738","GSM9039739","GSM9039728","GSM9039736","GSM9039725","GSM9039737","GSM9039726","GSM9039734","GSM9039735","GSM9039724","GSM9039732","GSM9039733","GSM9039730","GSM9039731","GSM9039729"],"GPL":["24247"],"GSE":["299488"],"taxon":["Mus musculus"],"PMID":["[41545197]"]}}