Aneuploidy, or an uneven number of chromosomes, has mostly detrimental consequences in eukaryotic cells, which include impaired proliferation as well as compromised DNA replication and protein folding. Unexpectedly, a new study published in this issue of The EMBO Journal shows that in murine embryonic stem cells aneuploidy does not interfere with proliferation, but rather hinders their differentiation capacity, thus propelling the formation of poorly differentiated teratomas.
See also: M Zhang et al (November 2016)
Maintaining genome integrity is an essential task for every cell and there are many ways in which things can go wrong. One of the most frequent errors affecting genome integrity is chromosome missegregation, which occurs at an estimated frequency of 1:1,000 in mitosis and even more often during meiosis. In the immediate response to chromosome segregation errors, most cells will irreversibly arrest, but surviving cells can give rise to an aneuploid population. Aneuploidy, a cellular state characterized by an unbalanced number of chromosomes, is the leading cause of spontaneous miscarriages and a hallmark of cancer. Yet, what makes aneuploidy so detrimental to cellular physiology has been difficult to tackle.
Recent years have witnessed an increased interest in aneuploidy fueled to a great degree by the establishment of novel cell models with simple defined aneuploidies. Over the past years, model systems from yeast, Drosophila, Arabidopsis as well as murine and human somatic cells have been established that gained a part or a whole chromosome and their phenotypes and physiology have been analyzed in comparison with their isogenic euploid counterparts. Most studies using these model systems revealed that a gain of even a single chromosome impairs proliferation and leads to globally altered gene expression, proteotoxic stress, …
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