The caudal dorsal artery generates hematopoietic stem and progenitor cells via the endothelial-to-hematopoietic transition in zebrafish.

ABSTRACT

Zebrafish hematopoietic stem and progenitor cells (HSPCs) originate from the hemogenic endothelium of the ventral wall of the dorsal aorta (DA) through the endothelial-to-hematopoietic transition (EHT) from approximately 30 to 60 hours post fertilization (hpf). However, whether other artery sites can generate HSPCs de novo remains unclear. In this study, using live imaging and lineage tracing, we found that the caudal dorsal artery (CDA) in the caudal hematopoietic tissue directly gave rise to HSPCs through EHT. This process initiated from approximately 60 hpf and terminated at approximately 156 hpf. Compared with that in the DA, fewer EHT events were observed in the CDA. The EHT events in the DA and CDA were similarly regulated by Runx1 but differentially influenced by blood flow (i.e., the EHT frequency in CDA was affected to a lesser extent when circulation was compromised in the tnnt2a-/- mutant). Therefore, the whole artery, including both DA and CDA, was endowed with the ability to produce HSPCs during a much longer time period. Coincidently, the lineage tracing results indicated that adult hematopoietic cells originated from the embryonic endothelium, and those produced later preferentially colonized the adult thymus. Collectively, our study revealed that the CDA serves as an additional source of hematopoiesis, and it shows similar but not identical properties with the DA.