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

Christine R Keenan; Michael J Mlodzianoski; Hannah D Coughlan; Naiara G Bediaga; Gaetano Naselli; Erin C Lucas; Qike Wang; Carolyn A de Graaf; Douglas J Hilton; Leonard C Harrison; Gordon K Smyth; Kelly L Rogers; Thomas Boudier; Rhys S Allan; Timothy M Johanson

doi:10.1016/j.isci.2021.102161

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

iScience. 2021 Feb 7;24(3):102161. doi: 10.1016/j.isci.2021.102161. eCollection 2021 Mar 19.

Authors

Christine R Keenan^{1

2}, Michael J Mlodzianoski^{1

2}, Hannah D Coughlan^{1

2}, Naiara G Bediaga^{1

2}, Gaetano Naselli^{1

2}, Erin C Lucas^{1

2}, Qike Wang^{1

2}, Carolyn A de Graaf^{1

2}, Douglas J Hilton^{1

2}, Leonard C Harrison^{1

2}, Gordon K Smyth^{1

3}, Kelly L Rogers^{1

2}, Thomas Boudier^{1

2

4}, Rhys S Allan^{1

2}, Timothy M Johanson^{1

2}

Affiliations

¹ The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.
² Department of Medical Biology, The University of Melbourne, Parkville, VIC, 3010, Australia.
³ School of Mathematics and Statistics, The University of Melbourne, Parkville, VIC, 3010, Australia.
⁴ Institute of Biology Paris-Seine, Sorbonne Université, Paris, France.

Abstract

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.

Keywords: chromosome organization; immunology; optical imaging; organizational aspects of cell biology.