GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE333nnn/GSE333596/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE333596GEOGSEfalseSingle-Cell RNA Sequencing Identifies Stem-Like Subpopulations and Their Gene Signature in Lung Adenocarcinoma ProgressionLung adenocarcinoma (LUAD) exhibits substantial intra-tumor heterogeneity (ITH), contributing to disease progression and therapeutic challenges. This study utilized single-cell RNA sequencing (scRNA-seq) to profile cells from stage I and III LUAD tumors and matched normal tissues, aiming to delineate malignant cell states and identify tumor-propagating subpopulations. Unsupervised clustering revealed eight major cell lineages, with epithelial cells dominating in tumors and a shift toward immunosuppressive niches in advanced stages, including elevated T cell exhaustion and pro-angiogenic macrophages. Malignant cells formed 11 subclusters, with stage III tumors enriched for invasive and immunosuppressive states. Pseudotime analysis suggested evolutionary trajectories from alveolar-like to squamous and stress-responsive lineages. Using CytoTRACE to infer stemness without predefined markers, we identified sub-cancer stem cells (sub-CSCs) predominantly in stage III, characterized by high transcriptional diversity and a core signature involving cytoskeleton motility, immune modulation, metabolic reprogramming, and protein homeostasis. A four-gene panel demonstrated strong prognostic value in independent cohorts. These findings provide insights into stemness-driven progression in LUAD and nominate potential targets for addressing heterogeneity.2026/07/31GSE333596GSM9769648GSM9769649GSM9769650GSM9769653GSM9769654GSM9769651GSM9769652GSM9769657GSM9769658GSM9769647GSM9769655GSM976965624676333596Homo sapiens