Tetraploidy-associated centrosome overduplication in mouse early embryos

Abstract

Recently, we observed that tetraploidization of certain types of human cancer cells resulted in upregulation of centrosome duplication cycles and chronic generation of the extra centrosome. Here, we investigated whether tetraploidy-linked upregulation of centrosome duplication also occurs in non-cancer cells using tetraploidized parthenogenetic mouse embryos. Cytokinesis blockage at early embryonic stage before de novo centriole biogenesis provided the unique opportunity in which tetraploidization can be induced without transient doubling of centrosome number. The extra numbers of the centrioles and the centrosomes were observed more frequently in tetraploidized embryos during the blastocyst stage than in their diploid counterparts, demonstrating the generality of the newly found tetraploidy-driven centrosome overduplication in mammalian non-cancer systems.

Chromosomal mosaicism: Origins and clinical implications in preimplantation and prenatal diagnosis

“…Endoduplication, where chromosomes are rereplicated without an intervening cellular division, failed cytokinesis, and overduplication of centrosomes have been linked to the formation of tetraploid cells (Figure 1e). 8 In some cases after failed cytokinesis, this may give rise to binucleate cells 3 . Tetraploidy is observed in human conceptuses, however, it also induces chromosomal instability, aneuploidy, and tumorogenesis in mouse embryos 9,10 .…”

“…Chromosomal aneuploidy brings with it major changes in gene dosage which typically has a catastrophic effect on this fine‐tuned process. Indeed, the primary effect of aneuploidy is embryonic and/or fetal lethality 1–8 . The greater the number of protein coding genes involved, the higher the chance the pregnancy will miscarry 1 …”

“…Indeed, the primary effect of aneuploidy is embryonic and/or fetal lethality. [1][2][3][4][5][6][7][8] The greater the number of protein coding genes involved, the higher the chance the pregnancy will miscarry. 1 With few exceptions, every somatic cell in the human body should have the same chromosome number and structure.…”

Ventx Family and Its Functional Similarities with Nanog: Involvement in Embryonic Development and Cancer Progression

“…Consequently, the allotetraploidy of Xenopus laevis genome has become an important model in which to study polyploidy and aneuploidy formation. Tetraploidy and aneuploidy have been reported as having associations with various kinds of diseases in humans, such as cancers, Parkinson’s, aging disorders, Alzheimer’s, and neuromuscular developmental disorders [ 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ].…”

Pcp1/pericentrin controls the SPB number in fission yeast meiosis and ploidy homeostasis

“…It is generally believed that, in tumors, extra centrosomes are acquired concomitantly with tetraploidization of the cells, but the mechanistic link between polyploidization and the formation of extra centrosomes is not fully understood ( Baudoin et al, 2020 ; Ganem et al, 2009 ; Storchova and Pellman, 2004 ). Studies in mouse early embryos have shown that tetraploidization, even without initial concomitant doubling of centrosomes, leads to the formation of extra centrosomes during subsequent cell division ( Yaguchi et al, 2018 ), suggesting that polyploidization may play a dominant role in centrosome quantity dysregulation. This series of evidence suggests that the interaction between MTOC number dysregulation and polyploidy is conserved among organisms.…”