The frequency and consequences of multipolar mitoses in undifferentiated embryonic stem cells

Veronika Pospíšilová (1) , Milan Ešner (1, 2) , Iveta Červenková (1) , Radek Fedr (3) , Jean-Yves Tinevez (4) , Aleš Hampl (1, 5) , Martin Anger (1, 2)

1 MED / MUNI - Department of Histology and Embryology [Brno]
2 CEITEC MU - Central European Institute of Technology [Brno]
3 IBP / CAS - Institute of Biophysics of the Czech Academy of Sciences
4 IAH - Hub d'analyse d'images - Image Analysis Hub (Platform)
5 St. Anne’s University Hospital [Brno]

Embryonic stem (ES) cells are pluripotent cells widely used in cell therapy and tissue engineering. However, the broader clinical applications of ES cells are limited by their genomic instability and karyotypic abnormalities. Thus, understanding the mechanisms underlying ES cell karyotypic abnormalities is critical to optimizing their clinical use. In this study, we focused on proliferating human and mouse ES cells undergoing multipolar divisions. Specifically, we analyzed the frequency and outcomes of such divisions using a combination of time-lapse microscopy and cell tracking. This revealed that cells resulting from multipolar divisions were not only viable, but they also frequently underwent subsequent cell divisions. Our novel data also showed that in human and mouse ES cells, multipolar spindles allowed more robust escape from chromosome segregation control mechanisms than bipolar spindles. Considering the frequency of multipolar divisions in proliferating ES cells, it is conceivable that cell division errors underlie ES cell karyotypic instability.

Keywords: Mitosis length; Multipolar division; Embryonic stem (ES) cells; Single-cell tracking; Spindle assembly checkpoint (SAC); Time-lapse microscopy

Domains: Life Sciences [q-bio]

Veronika Pospíšilová, Milan Ešner, Iveta Červenková, Radek Fedr, Jean-Yves Tinevez, et al.. The frequency and consequences of multipolar mitoses in undifferentiated embryonic stem cells. Journal of Applied Biomedicine, 2019, 17 (4), pp.209-217. ⟨10.32725/jab.2019.018⟩. ⟨pasteur-02616481⟩