{
  "abstract": "Lung adenocarcinoma (LUAD) demonstrates significant intra-tumor heterogeneity (ITH), which plays a critical role in disease progression and complicates therapeutic interventions. In the present study, we employed single-cell RNA sequencing (scRNA-seq) to analyze cellular populations derived from stage I and stage III LUAD tumors, alongside matched adjacent normal tissues, with the objective of delineating malignant cell states and identifying tumor-propagating subpopulations. Unsupervised clustering analysis identified eight principal cell lineages, with epithelial cells predominating within tumor samples. Notably, advanced-stage tumors demonstrated a shift toward an immunosuppressive microenvironment, characterized by elevated T cell exhaustion and an increased presence of pro-angiogenic macrophages. Further stratification of malignant cells revealed eleven distinct subclusters, with stage III tumors enriched for invasive and immunosuppressive phenotypes. Pseudotime trajectory analysis identified evolutionary transitions from alveolar-like states toward squamous and stress-responsive lineages. Employing CytoTRACE to evaluate stemness independently of predefined markers, we identified subpopulations of cancer stem cells (sub-CSCs) predominantly in stage III tumors. These sub-CSCs exhibited heightened transcriptional heterogeneity and a core gene signature associated with cytoskeletal motility, immune regulation, metabolic reprogramming, and protein homeostasis. A four-gene panel derived from this signature demonstrated robust prognostic significance in independent LUAD cohorts. Collectively, these findings enhance the current understanding of stemness-driven tumor progression in LUAD and suggest potential therapeutic targets to address tumor heterogeneity.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "name": "Lijuan Shao"
    },
    {
      "name": "Jiali Guo"
    },
    {
      "name": "Yujia Chen"
    },
    {
      "name": "Hua Wu"
    },
    {
      "name": "Yanming Zhong"
    },
    {
      "name": "Jiayi Dong"
    },
    {
      "name": "Wenxin Huang"
    },
    {
      "name": "Yanfeng Sun"
    },
    {
      "name": "Junzheng Yang"
    },
    {
      "name": "Size Chen"
    },
    {
      "name": "Qian He"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c35hqq6ztmt94.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1935165",
  "fulltext_url": null,
  "id": "c35hqq6ztmt94",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1935165",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "feed-journal",
      "medicine/pharmacology-toxicology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-04",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/c35hqq6ztmt94.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:20:50Z",
      "native_id": "10.3389/fphar.2026.1935165",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1935165"
    },
    {
      "first_seen": "2026-11-04T12:21:43Z",
      "native_id": "10.3389/fphar.2026.1935165",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1935165/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "feed-journal:medicine/pharmacology-toxicology",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Single-cell RNA sequencing identifies stem-like subpopulations and their gene signature in lung adenocarcinoma progression",
  "title_text": "Single-cell RNA sequencing identifies stem-like subpopulations and their gene signature in lung adenocarcinoma progression",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T00:21:25Z",
  "url": "https://research.draconitic.com/paper/c35hqq6ztmt94",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}