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Polyclonal-to-monoclonal transition in colorectal precancerous evolution
Zhaolian Lu1,2, Shanlan Mo1,2, Duo Xie1,3
1Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Nature
|October 31, 2024
Summary
Colorectal precancer often starts with multiple cell lineages cooperating, evolving into single lineages in later stages. Understanding these early interactions offers new opportunities for cancer prevention.
Area of Science:
- Oncology
- Genetics
- Cell Biology
Background:
- Understanding precancerous lesion evolution is key for cancer prevention.
- Current knowledge of early cancer development is limited.
Purpose of the Study:
- To map single-cell phylogenies in intestinal tumorigenesis models.
- To investigate the origins and evolution of colorectal precancer.
Main Methods:
- Utilized a base editor-enabled DNA barcoding system for single-cell phylogeny mapping.
- Analyzed high-resolution phylogenies of 260,922 cells from mouse intestinal tissues.
- Performed bulk whole-exome and single-gland whole-genome sequencing on human colorectal polyps.
Main Results:
- Identified tens of independent cell lineages undergoing parallel clonal expansion in lesions.
- Revealed polyclonal origins for human sporadic colorectal polyps.
- Observed a transition from polyclonal to monoclonal lesions, with monoclonal representing a later stage.
- Found extensive intercellular interactions in early polyclonal lesions, decreasing during monoclonal transition.
Conclusions:
- Colorectal precancer is frequently initiated by multiple cooperating cell lineages.
- Cooperative interactions are crucial in the earliest stages of cancer formation.
- Findings suggest potential for earlier intervention in colorectal cancer development.
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