Deciphering the generation of heterogeneity in esophageal squamous cell carcinoma metastasis via single-cell multiomics analysis

• DOI: 10.1186/s12967-025-06154-6
• Publication Date: 2025-02-04T07:37:11Z
• Authors: Kaiwen Sheng; Jun Chen; Ruitang Xu; Haoqiang Sun; Ran Liu; Yongjie Wang; Wenwen Xu; Jiao Guo; Miao Zhang; Shuai Liu; Juan Lei; Yawen Sun; Yang Jia; Dianhao Guo
• Keywords: SERPINH1; Tumor heterogeneity; Tumor microenvironment; Research; R; Medicine; scATAC-seq; Single-cell multiomic analysis; Gene regulation

Chromatin accessibility plays a crucial role in mediating transcriptional dysregulation and heterogeneity Esophageal Squamous Cell Carcinoma (ESCC). Examining the chromatin of ESCC at single-cell level is imperative to understand how it activates oncogenes contributes onset metastasis ESCC. We performed assay for transposase-accessible sequencing (scATAC-seq) on cancerous adjacent noncancerous tissues from four patients who were pathological staged as T1a, T2b, T3b, or T4a, investigate whether regulatory elements are pivotal instigating cellular during metastasis. In conjunction, we integrated these data with 55 scRNA-seq datasets, ChIP-seq CUT&Tag data, Hi-C bulk RNA-seq ATAC-seq cell lines dissect mechanisms underlying tumor microenvironment (TME). Our study identified enhancer-specific activation within epithelial cells orchestrated by three-dimensional structure that regulates SERPINH1 transcription, promotes epithelial-mesenchymal transition (EMT) Additionally, element facilitated expression TNFSF4 CD8 + exhausted T cells, thereby activating Tregs. Furthermore, observed promoted differentiation tumor-associated macrophages (TAMs) cancer associated fibroblasts (CAFs). summary, utilizing multiomics analyses, have revealed maps illuminated intricate molecular underlie metastasis, offering valuable insights further advance research progression deterioration.