Dendritic cells (DCs) are crucial in both innate immunity and acquired immunity. They are known to be derived exclusively from hematopoietic stem cells (HSCs). However, in a new study, Zilong Wen and colleagues identify a distinct DC population in zebrafish that originates independently of HSCs. These cells colonize the developing thymus at an earlier stage compared to the HSC-derived DCs.
Due to lack of a suitable zebrafish reporter for DCs, the researchers use an RNA-scope approach to identify the presence of DCs in the thymus as early as 3 days post-fertilization. To investigate the origin of DCs, they employ cell-fate mapping to trace the lineages of DCs from embryonic to adult stages. The findings reveal the presence of two distinct waves of dendritic cell development: an initial transient wave originating early from dorsal aorta-born endothelium-derived hematopoietic progenitors and diminishing gradually during juvenile stages, and a subsequent wave derived from HSCs that populates different tissues and persists into adulthood. Furthermore, the researchers observe that the two populations have different dependencies on Fms-like tyrosine kinase 3, a receptor tyrosine kinase essential for dendritic cell development. Collectively, these findings highlight the presence of two distinct dendritic cell populations with diverse origins and distinct developmental regulations.