Profiling cell proliferation after whole-genome duplication in human cells

Area of Science:

• Cell Biology
• Genetics
• Cancer Research

Background:

• Whole-genome duplication (WGD) is a hallmark of many cancers, yet the mechanisms governing post-WGD cell proliferation and genomic stability remain poorly understood.
• Understanding how cells with duplicated genomes divide is crucial for deciphering cancer progression and developing targeted therapies.

Purpose of the Study:

• To investigate the proliferation dynamics and mitotic patterns of post-whole-genome duplication (WGD) HCT116 cell lineages.
• To identify key cellular events that dictate the proliferative capacity and fate of cells following WGD.

Main Methods:

• Utilized 6-day live-imaging to track over 150 post-WGD HCT116 cell lineages.
• Performed quantitative comparisons of mitotic patterns and cell fates between proliferative and non-proliferative lineages.
• Analyzed chromosome segregation events and their correlation with cell viability and proliferation.

Main Results:

• Multipolar chromosome segregation in early mitosis was identified as a critical factor limiting the proliferation of post-WGD cells.
• The frequency and severity of multipolar segregation, especially with significant chromosome loss, correlated with reduced cell viability.
• Proliferative lineages managed WGD by strategically allocating multipolar segregation risk to sub-lineages or through adaptation to early multipolar events.

Conclusions:

• Key cellular events, particularly multipolar chromosome segregation, govern the proliferation dynamics and diversity observed in post-WGD cells.
• These findings provide fundamental insights into the biological consequences of WGD and its role in cancer evolution.
• The study offers a reference for understanding WGD-associated biological processes and potential therapeutic vulnerabilities.