Multifunctional barcoding with ClonMapper enables high-resolution study of clonal dynamics during tumor evolution and...

Area of Science:

• Cancer Biology
• Genomics
• Molecular Biology

Background:

• Lineage-tracing is crucial for understanding clonal dynamics in complex cell populations.
• Existing methods struggle to integrate multi-omic data with live-cell manipulation of specific clones.

Purpose of the Study:

• To develop a novel lineage-tracing system, ClonMapper, for comprehensive clonal analysis.
• To integrate DNA barcoding, single-cell RNA sequencing, and clonal isolation.
• To characterize clonal heterogeneity and therapeutic responses in chronic lymphocytic leukemia.

Main Methods:

• Developed ClonMapper, a functionalized lineage-tracing system.
• Integrated DNA barcoding with single-cell RNA sequencing (scRNA-seq).
• Enabled clonal isolation for detailed analysis before, during, and after treatment.

Main Results:

• Identified distinct subpopulations in a chronic lymphocytic leukemia (CLL) cell line.
• Characterized unique transcriptional signatures and chemotherapy survivorship trajectories for these subpopulations.
• Observed similar patterns in primary human CLL samples.
• Enabled direct measurement of clonal diversification and transcriptional signatures post-treatment.

Conclusions:

• ClonMapper is a powerful, multifunctional tool for dissecting complex clonal dynamics.
• The system facilitates comprehensive characterization of tumor progression and therapeutic response.
• Revealed critical insights into CLL heterogeneity and treatment resistance mechanisms.