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Updated: Aug 10, 2025
10:55
Live Imaging Followed by Single Cell Tracking to Monitor Cell Biology and the Lineage Progression of Multiple Neural Populations
Published on: December 16, 2017
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Integration of multiple lineage measurements from the same cell reconstructs parallel tumor evolution.
Lennart Kester1, Buys de Barbanson1,2, Anna Lyubimova1
1Oncode Institute, Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences), 3584 CT Utrecht, the Netherlands.
Cell Genomics
|February 13, 2023
Summary
This study used colon cancer organoids and single-cell sequencing to track tumor evolution over six months. Researchers identified recurrent chromosome 4 and 18 loss, a key finding for understanding colorectal cancer progression.
Area of Science:
- Cancer Biology
- Genomics
- Evolutionary Biology
Background:
- Intra-tumor heterogeneity (ITH) and tumor evolution are critical challenges in cancer research.
- Organoid models offer a promising platform for studying these complex processes.
- Single-cell sequencing technologies enable high-resolution analysis of cellular diversity within tumors.
Purpose of the Study:
- To reconstruct colon cancer evolution at high resolution using organoid models.
- To identify the order and recurrence of genomic aberrations during tumor development.
- To investigate the clinical relevance of observed genomic events in colorectal cancer.
Main Methods:
- Evolved a colon cancer organoid model for 100 generations (6 months).
- Integrated single-cell whole-genome sequencing (WGS) and viral lineage tracing.
- Analyzed 1,641 single cells across 12 time points for clone size, SNVs, CNVs, and viral barcodes.
Main Results:
- Constructed high-resolution clonal evolution trees.
- Characterized the sequential order of chromosomal aberrations.
- Observed recurrent loss of chromosome 4 after chromosome 18 loss in four distinct tumor clones.
- Validated SNV and CNV findings against a colorectal cancer patient cohort, noting 29.6% co-occurrence of chromosome 4 and 18 loss.
Conclusions:
- Organoid evolution models with integrated single-cell sequencing provide a powerful approach to study tumor evolution.
- Identified a potentially clinically relevant recurrent genomic aberration (chr18 loss followed by chr4 loss) in colorectal cancer.
- This methodology can identify significant genomic events driving tumor development and heterogeneity.
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