Abstract 7490: Uncovering rare cellular populations in esophageal preneoplasia through genetic perturbation tracking and scRNA-seq

Abstract The early detection and characterization of rare cellular populations in preneoplastic lesions are crucial for understanding cancer initiation and progression, as well as for identifying novel therapeutic targets. Rare cell populations, often overlooked due to their low abundance, play pivotal roles in shaping the tumor microenvironment and driving disease development. In this study, we employed a lineage tracing system based on tracing vectors introduced into a 2D cell line model of esophageal preneoplasia. This approach allowed us to track genetic perturbations that accumulate during cell proliferation, enabling precise identification of distinct cellular lineages. By coupling this lineage tracing method with single-cell RNA sequencing (scRNA-seq), we achieved high-resolution transcriptomic profiling, uncovering rare cellular populations with unique molecular and lineage-specific characteristics. The rare populations identified through this integrated approach exhibited a quiescent phenotype, suggesting their involvement in lesion persistence and resistance to therapies targeting proliferative cells. Transcriptomic analysis revealed distinct genetic signatures and key pathways associated with these populations, offering potential avenues for therapeutic intervention and biomarker development. Our findings demonstrate the value of combining genetic perturbation-based lineage tracing with scRNA-seq to uncover rare and functionally significant cellular populations. This study provides new insights into the cellular dynamics underlying esophageal cancer initiation and progression, laying the groundwork for future research aimed at understanding the roles of these populations and developing targeted therapies. Citation Format: Jinho Jang, Kyung-Pil Ko, Jie Zhang, Jae-Il Park. Uncovering rare cellular populations in esophageal preneoplasia through genetic perturbation tracking and scRNA-seq [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7490.