A marker-independent lineage-tracing system to quantify clonal dynamics and stem cell functionality in cancer tissue

Area of Science:

• Oncology
• Stem Cell Biology
• Bioengineering

Background:

• Lineage tracing is crucial for understanding cell fate and dynamics.
• Cancer stem cells (CSCs) drive tumor growth and recurrence, but their specific markers are not fully understood.
• Quantitative analysis of clonal dynamics is essential for cancer research.

Purpose of the Study:

• To present a novel method for quantitative analysis of clonal dynamics in grafted cancer tissues.
• To assess stem cell functionality and infer tumor expansion dynamics independently of molecular markers.
• To enable quantification of clonal advantages conferred by specific mutations, with or without therapeutic intervention.

Main Methods:

• Preparation and validation of cells for lineage tracing.
• Establishment of cancer grafts and induction of lineage labels.
• Analysis of clone-size distribution and fitting data to a mathematical tumor growth model.
• Utilizing an experimental system and analytical framework for quantitative assessment.

Main Results:

• The method allows for quantitative analysis of clonal dynamics in grafted cancer tissues.
• Stem cell functionality and tumor expansion dynamics are inferred without relying on CSC-specific genes.
• The system can quantify clonal advantages from mutations in both untreated and treated cancer models.

Conclusions:

• This novel protocol provides a robust framework for studying cancer clonal dynamics and stem cell functionality.
• The method's independence from molecular markers offers a versatile approach to cancer research.
• The developed analytical framework aids in understanding tumor growth and the impact of mutations and therapies.