Genetic and Epigenetic Phenomena in the Neutrophil Developmental Program

Neutrophils are short-lived innate immune cells, which develop in the bone marrow and replenish daily the circulatory and marginal pools in various organs in the steady state. Recent technological advances have reshaped the traditional paradigms for neutrophil biology and have identified intriguing (epi)genetic phenomena associated with their differentiation, maturation and function. Herein we summarise these developments and discuss: the new model for instructed programming of neutrophil development and continuous cell development via the lineage trajectory path; new aspects of epigenetic regulation of neutrophil development and in particular changes in chromatin structure, 3D architecture as well as heterochromatin condensation during nuclear segmentation; the remarkable breadth of neutrophil heterogeneity and the atypical function of neutrophils acting as antigen-presenting cells. Understanding these concepts can advance the design of new models of in vitro neutrophil generation and drug discovery in immune-mediated disease and cancer where neutrophils play important roles in the pathogenesis.