Abstract A005: Investigating the role of stabilin-2 in hematopoietic stem and progenitor cell emergence and migration in zebrafish
Hematopoietic stem cell transplantation is a critical yet high risk therapeutic treatment for patients with blood and immune disorders, including those with cancer where the bone marrow can be severely compromised due to malignancy, intensive chemotherapy and radiation. Despite its potential to restore hematopoietic function and immune health, the procedure leaves patients immunocompromised and vulnerable to dangerous infections until the donor hematopoietic stem and progenitor cells (HSPCs) engraft in the recipient’s bone marrow niche and regenerate their blood and immune system. Recently, we identified a conserved gene expression signature unique to sinusoidal endothelial cells of HSPC niches in fish and mammals, which includes specific membrane trafficking machinery and the scavenger receptor, Stabilin-2 (stab2). In other cellular contexts, stab2 is known to engage in both cell adhesion and endocytic functions. To determine the function of stab2 in the niche, we used CRISPR/Cas9 to knock out stab2 in zebrafish embryos and observed fewer HSPCs in the niche of stab2 mutants compared to sibling controls. To determine whether this reduction results from a defect in HSPC formation we used live, high resolution confocal microscopy to quantify the number of HSPCs forming in their site of birth in the Aorta Gonad Mesenpheros. We found no difference in the number of HSPCs that formed in stab2 mutants compared to their sibling controls. This data suggests that other mechanisms (e.g. defects in proliferation or niche migration) lead to fewer HSPCs in the niche in stab2 mutants. Collectively, these observations advance our basic understanding of the HSPC niche and could allow us to inform future clinical strategies to improve HSPC expansion ex vivo. Reema A . Elrefaie, Gwendolyn M. Beacham, Zewde Q . Ingram, Elliott J. Hagedorn. Investigating the role of stabilin-2 in hematopoietic stem and progenitor cell emergence and migration in zebrafish [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Breaking Barriers in the Fight against Rare Cancers; 2026 Jul 18-20; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(14_Suppl):Abstract nr A005.