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Deciphering Precursor Cell Dynamics in Esophageal Preneoplasia via Genetic Barcoding and Single-Cell Transcriptomics
Jinho Jang1, Kyung-Pil Ko1, Jie Zhang1
1Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Biorxiv : the Preprint Server for Biology
|March 10, 2025
Summary
Researchers mapped preneoplastic esophageal cell lineages using a novel tool. They identified preneoplastic precursor cells (PNPCs) as key drivers of early cancer, offering new biomarkers for esophageal cancer detection.
Area of Science:
- Oncology
- Cell Biology
- Genetics
Background:
- Cancer cell heterogeneity and plasticity complicate tumorigenesis research and therapy development.
- Preneoplastic cells, though appearing normal, exhibit plasticity and early genetic changes, but their origins are unknown.
Purpose of the Study:
- To map preneoplastic esophageal cell lineages and identify their origins and trajectories.
- To develop novel tools for lineage tracing and identifying high-plasticity cells in early cancer development.
Main Methods:
- Developed a lineage-tracing tool combining genetic barcoding with single-cell RNA sequencing.
- Introduced the eXamined Ridge (XR) score to accurately identify high-plasticity cells.
- Analyzed transcriptional profiles and identified marker genes in preneoplastic cells.
Main Results:
- Identified preneoplastic precursor cells (PNPCs) as a distinct progenitor-like population with high plasticity.
- PNPCs contribute to proliferative and basal cell populations in the esophagus.
- Discovered conserved PNPC markers, Nfib and Qk, which are prominent in early preneoplasia and decrease upon malignant transformation.
Conclusions:
- PNPCs are crucial players in early esophageal tumorigenesis.
- PNPCs and their markers hold potential as biomarkers for early cancer detection and therapeutic strategies.
- Findings offer new approaches for preventing esophageal cancer progression.
