Chromosomes distribute randomly to, but not within, human neutrophil nuclear lobes

Abstract

The proximity pattern and radial distribution of chromosome territories within spherical nuclei are well understood to be random and non-random, respectively. Whether this distribution pattern is conserved in the partitioned or lobed nuclei of polymorphonuclear cells is unclear. Here we use chromosome paint technology and a novel high-throughput imaging analysis pipeline to examine the chromosome territories of all 46 chromosomes in hundreds of single human neutrophils - an abundant and famously polymorphonuclear immune cell. By comparing the distribution of chromosomes to randomly shuffled controls, and validating with orthogonal chromosome conformation capture technology, we show for the first time that all human chromosomes randomly distribute to neutrophil nuclear lobes, while maintaining a non-random radial distribution within these lobes. Furthermore, by leveraging the power of this vast dataset, we are able to reveal characteristics of chromosome territories not detected previously. For example, we demonstrate that chromosome length correlates with three-dimensional volume not only in neutrophils but other human immune cells. This work demonstrates that chromosomes are largely passive passengers during the neutrophil lobing process, but are able to maintain their macro-level organisation within lobes. Furthermore, the random distribution of chromosomes to the naturally partitioned nuclear lobes suggests that specific transchromosomal interactions are unimportant in mature neutrophils.