BioProject

Background. Mammalian cells are flexible and can rapidly change shape when they contract, adhere, or migrate. More...

Background. Mammalian cells are flexible and can rapidly change shape when they contract, adhere, or migrate. Their nucleus must be stiff enough to withstand cytoskeletal forces, but flexible enough to remodel as the cell changes shape. This is particularly important for cells migrating through constricted space, where the nuclear shape must change in order to fit through. This happens many times in the life cycle of a neutrophil, which must protect its chromatin from damage and disruption associated with migration. Results. Total RNA-sequencing identified that neutrophil migration through 5 or 14 µm pores was associated with changes in the transcript levels of inflammation and chemotaxis-related genes, when compared to unmigrated cells. Differentially expressed transcripts specific to migration with constriction were enriched for groups of genes associated with cytoskeleton remodelling. Hi-C was used to capture the genome organisation in control and migrated cells. Chromatin did not switch between the active (A) and inactive (B) compartments after migration. However, global depletion of mid- to long-range contacts was observed following active migration through the 5 µm pores. Chromatin contacts that decreased in frequency were enriched in inactive chromatin. Conclusion. Mid- to long-range contacts are preferentially lost within inactive chromatin, thus protecting transcriptionally active contacts from the disruptive effects of migration with constriction. This is consistent with current hypotheses implicating heterochromatin as the mechanoresponsive form of chromatin. Further investigation concerning the contribution of heterochromatin to stiffness, flexibility, and protection of nuclear function will be important for understanding cell migration in human health and disease. Overall design: Total RNA sequencing in triplicate of neutrophil-like cells migrated through large (14µm) or small (5µm) pores, with an unmigrated control population. Less...