The endothelial scavenger receptor stab2 is required for proper hematopoietic stem and progenitor cell development in the fetal blood stem cell niche

Abstract

Hematopoietic stem and progenitor cell (HSPC) niches support lifelong production of blood and immune cells. Recently, we identified a gene signature unique to HSPC niche endothelial cells that is highly conserved across species and developmental time and includes the scavenger receptors stab1/2 and mrc1a. Whether these receptors support HSPC development remains unclear. To investigate this, we used chemical inhibition and CRISPR mutagenesis in zebrafish and found that loss of stab2, and to a lesser degree stab1, reduced the number of embryonic runx1(+) HSPCs. Subsequent analyses of an additional HSPC marker (cd41) revealed an imbalance in the HSPC pool in stab2 mutants, with reductions in runx1(+)cd41(+) and runx1(+)cd41(-) sub-populations containing stem cells and erythroid progenitors, respectively, the latter of which was most decreased. Our findings suggest stabilin scavenger receptors support HSPC development in the fetal niche, which could inform clinical strategies for culturing and expanding HSPCs.