Inflammatory cytokines provide both infection-responsive and developmental signals for blood development: Lessons from the zebrafish

• Inflammatory signaling pathways influence HSC function during infection.
• Sterile inflammatory signaling pathways help orchestrate HSC production within the embryo.
• The zebrafish model is ideally suited to investigate inflammatory processes and HSC biology.
• Research using the zebrafish has uncovered new mechanistic insight into how inflammatory signaling pathways influence the HSC compartment.

Hematopoietic stem cells (HSCs) are rare, largely dormant, long-lived cells that are capable of establishing and regenerating all mature blood cell lineages throughout the life of the host. Given their therapeutic importance, understanding factors that regulate HSC development and influence HSC proliferation and differentiation is of great interest. Exploring HSC biology through the lens of infection has altered our traditional view of the HSC. The HSC can now be considered a component of the immune response to infection. In response to inflammatory cytokine signaling, HSCs enhance their proliferative state and contribute to the production of in-demand blood cell lineages. Similar cytokine signaling pathways also participate during embryonic HSC production. With its highly conserved hematopoietic system and experimental tractability, the zebrafish model has made significant contributions to the hematopoietic field. In particular, the zebrafish system has been ideally suited to help reveal the molecular and cellular mechanisms underlying HSC development. This review highlights recent zebrafish studies that have uncovered new mechanistic insights into how inflammatory signaling pathways influence HSC behavior during infection and HSC production within the embryo.