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

Abstract

Summary The proximity pattern and radial distribution of chromosome territories within spherical nuclei are 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 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 human chromosomes randomly distribute to neutrophil nuclear lobes, while maintaining a non-random radial distribution within these lobes. Furthermore, 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 subsequently maintain their macro-level organization within lobes.

Current Understanding of the Neutrophil Transcriptome in Health and Disease

“…Certainly, it is becoming accepted that the low basal transcriptional activity by neutrophils is not a consequence of the segmented structure preventing chromosomal organisation, another long held assumption of neutrophil biology. Although the distribution of chromosomes to the neutrophils lobes is random [30], distribution within lobes is non-random and radial based upon chromosome size as seen in regular spherical nuclei [30]. Super-resolution microscopy has now shown that chromatin in neutrophils is extremely compacted at the lobe peripheries, in contrast to the loosely arranged networks seen in precursor cells and somatic cells with spherical nuclei [31].…”

Heterochromatin and Polycomb as regulators of haematopoiesis

“…An additional dimension in heterochromatin regulation of haematopoiesis is the biophysical link between heterochromatin and the nuclear lamina which is thought to provide structural support to the nucleus and to protect the genome from damage. Our recent studies suggest the stability of heterochromatin at the nuclear periphery also has an important gene regulatory function supporting gene transcription in euchromatic regions [ 31 ], and that this peripheral localisation of heterochromatin may also guide the three-dimensional positioning of chromosomes into multi-lobed neutrophil nuclei [ 32 ]. Interestingly, a recent study has shown that the nuclei of HSCs undergo dramatic morphological changes during myeloid or lymphoid differentiation [ 33 ].…”