WNT5A from the fetal liver vascular niche supports human fetal liver hematopoiesis

The human fetal liver is a critical organ for prenatal hematopoiesis, the study of which offers insights into niche signals that regulate the fates of hematopoietic stem and progenitor cells (HSPCs) during fetal development. Here, we demonstrate that human fetal liver endothelium uniquely supports the maturation and expansion of multilineage HSPCs. Specifically, co-culture of fetal liver-derived immature CD43(+)CD45(-) hematopoietic cells with human fetal liver endothelial cells (ECs) led to a profound increase in the numbers of phenotypic CD45(+)CD34(+) HSPCs and multilineage colony-forming progenitors generated in vitro, when compared to co-culture with ECs derived from other organs. We further identified a supportive role for EC-derived WNT5A in this process via gain- and loss-of-function studies within ECs. Our study emphasizes the importance of the organ-specific endothelial niche in supporting hematopoietic development and provides novel insight into signals that may facilitate HSPC expansion in vitro for clinical applications.

Automated summary

The human fetal liver endothelium plays a unique role in supporting the maturation and expansion of multilineage hematopoietic stem and progenitor cells, with EC-derived WNT5A identified as a key factor in this process. The study highlights the significance of organ-specific endothelial niche in hematopoietic development and provides insights into potential signals for HSPC expansion in clinical applications.