Unfused Daughter Cells From Multipolar Mitoses Are Responsible For Chromosome Instablility In Hela Cells

Karyotypic heterogeneity, composed by aneuploidy of various chromosome complements, represents a common feature of a majority of cancers and is the driving force for tumors to constantly evolve and drug resistance. Chromosome instability (CIN) is a major source of these heterogeneous aneuploidies. Various defects, including compromised spindle assembly checkpoint, merotelic attachment and multipolar mitosis have been proposed to be responsible for the generation of aneuploidy and / or CIN. However, there are few systematic studies to validate these notions. In this study, using long-term live cell imaging combined with fluorescence in situ hybridization (FISH), we found daughter cells with abnormal chromosome complements were generated from multipolar mitosis with chromosomes segregating in an obligate disjunction manner in HeLa cells. Daughter cells from multipolar mitosis are prone to fusing into bi- or multi-nucleated cells. Fused cells (Bi- or multi-nucleated cells) died or underwent a subsequent round of multipolar mitosis. Only the mono-nucleated products of multipolar mitosis underwent normal-like bipolar mitosis, thus could stably pass the genetic material from one generation to another and have long term survival ability. Clone formation assay showed a small fraction of daughter cells from multipolar mitosis could grow into a lineage. Taken together, unfused daughter cells from multipolar mitosis could contribute to chromosome instability in HeLa cells.