Abstract
Any given cell type has an associated “normal” nuclear morphology, which is important to maintain proper cellular functioning and safeguard genomic integrity. Deviations from this can be indicative of diseases such as cancer or premature aging syndrome. To accurately assess nuclear abnormalities, it is important to use quantitative measures of nuclear morphology. Here, we give an overview of several nuclear abnormalities, including micronuclei, nuclear envelope invaginations, blebs and ruptures, and review the current methods used for image-based quantification of these abnormalities. We discuss several parameters that can be used to quantify nuclear shape and compare their outputs using example images. In addition, we present new pipelines for quantitative analysis of nuclear blebs and invaginations. Quantitative analyses of nuclear aberrations and shape will be important in a wide range of applications, from assessments of cancer cell anomalies to studies of nucleus deformability under mechanical or other types of stress.
Highlights
While multiple cellular factors are required to maintain nuclear genome integrity and organisation, a primordial role is played by the nuclear envelope (NE)
While not strictly describing nuclear shape, it is worth noting that a number of quantitative parameters of nuclear size can indirectly reflect the presence of NE defects and are often easier to compute in commonly used image analysis software packages
The past decades have seen an increase in the quantity of research on the mechanobiology of the nucleus, due to its emerging links with diseases such as cancer and premature aging syndromes
Summary
While multiple cellular factors are required to maintain nuclear genome integrity and organisation, a primordial role is played by the nuclear envelope (NE). Cells moving through constricted spaces (such as metastatic cancer cells travelling through tiny blood vessels) undergo dramatic nuclear shape changes [6,7,8,9]. These changes accompany gene regulatory events such as chromatin decondensation during transcription regulation. While all of these changes to the nuclear integrity occur at a low frequency in normal, healthy cells, they can dramatically increase in conditions where the NE integrity becomes challenged This can occur upon mechanical stress or when the NE structure is weakened by depletion or mutations of NE proteins.
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