[대학원 생명과학과 세미나 안내]
연사 : 최정민 교수(고려대학교 의과대학)
연제 : Spatiotemporally Resolved Single-cell Analyses Delineate Early Esophageal Squamous Carcinogenesis
일시 : 2022년 11월 25일 (금) 오후 4시 30분
장소 : 하나과학관 A동 109호
초청교수 : 지성욱 교수
Abstract
Esophageal squamous cell carcinoma (ESCC), the most prevalent histotype of esophageal neoplasm, has 5-year survival rates of 15-20%. Understanding the progression from normal, squamous dysplasia and invasive carcinoma is critical for both early detection and treatment. Here, we combined single-nucleus RNA-seq (snRNA-seq) with spatially resolved transcriptomics to decipher molecular differences between premalignant lesions compared with normal tissue and invasive tumor. Using patient samples, we constructed a cellular atlas of ESCC and discovered a novel tumor-initiating subpopulation in the epithelial compartment. Spatiotemporal pseudotime analysis revealed a distinct tumor cell lineage that was directly derived from a basal progenitor cell. Moreover, we identified that the composition of the immune compartment significantly changed at the stage of dysplasia, suggesting immune activation and evasion occur before tumor invasion. We further developed robust methods for an integrated analysis to better characterize spatial information at the single-cell level. Spot deconvolution using annotated snRNA-seq data not only reconstructed a priori knowledge of cancer pathobiology but also identified novel features of ESCC tumorigenesis with enhanced resolution. Finally, the interaction between tumor cells and immune/stromal cells could be mapped and visualized in the spatial context. These data define ESCC tumor and immune cell subpopulations during carcinogenesis, the spatial niches where they interact, and the dynamic gene expression reprogramming engaged in multi-compartments of cancer. Furthermore, these multimodal approaches may popularize near future to gain insights into individual tumor biology and their implementation in clinics.