Ontogenetically distinct neutrophils differ in function and transcriptional profile in zebrafish

Neutrophil ontogeny in zebrafish may be a continuum or consist of distinct lineages. Here the authors characterise neutrophils derived from rostral blood island and caudal haematopoietic tissue lineages and show differential gene expression and function in steady state and during wound healing. The current view of hematopoiesis considers leukocytes on a continuum with distinct developmental origins, and which exert non-overlapping functions. However, there is less known about the function and phenotype of ontogenetically distinct neutrophil populations. In this work, using a photoconvertible transgenic zebrafish line; Tg(mpx:Dendra2), we selectively label rostral blood island-derived and caudal hematopoietic tissue-derived neutrophils in vivo during steady state or upon injury. By comparing the migratory properties and single-cell expression profiles of both neutrophil populations at steady state we show that rostral neutrophils show higher csf3b expression and migration capacity than caudal neutrophils. Upon injury, both populations share a core transcriptional profile as well as subset-specific transcriptional signatures. Accordingly, both rostral and caudal neutrophils are recruited to the wound independently of their distance to the injury. While rostral neutrophils respond uniformly, caudal neutrophils respond heterogeneously. Collectively, our results reveal that co-existing neutrophils populations with ontogenically distinct origin display functional differences.

Automated summary

This study characterizes the developmental origins and functional differences of neutrophils derived from rostral blood island and caudal haematopoietic tissue lineages in zebrafish. The result shows that rostral neutrophils exhibit higher expression of csf3b and migration capacity compared to caudal neutrophils in steady state. Both populations have a core transcriptional profile upon injury, but caudal neutrophils respond heterogeneously. These findings reveal the functional differences of co-existing neutrophil populations with distinct developmental origins.