Overlapping roles for endothelial selectins in murine hematopoietic stem/progenitor cell homing to bone marrow

Abstract

Selectins are carbohydrate-binding adhesion molecules critically involved in leukocyte recognition of endothelium. The endothelial selectins have been implicated in homing of hematopoietic stem/progenitor cell(s) (HSPC) to the bone marrow (BM) during bone marrow transplant (BMT), but the precise role(s) of individual selectins in this process have never been defined. BMT of lethally irradiated mice lacking both endothelial selectins (E/P KO) with limiting numbers of wild-type BM cells rescued significantly fewer E/P KO than WT recipients, but higher numbers of transplanted WT cells rescued E/P KOs in a dose-dependent fashion. Short term homing assays confirmed a substantial defect in HSPC homing to BM in E/P KO mice. In contrast, BMT of E-selectin null (E KO) or P-selectin null (P KO) mice at limiting cell number uniformly rescued >95% of the transplanted animals. Consistent with these functional results, flow cytometric analysis revealed both E-selectin ligands and P-selectin ligands on distinct subsets of HSPC. Taken together, these results demonstrate overlapping functions for the endothelial selectins in HSPC homing to BM in the setting of BMT, and define a novel aspect of HSPC heterogeneity linked to selectin ligand expression.

The role of CD44 in fetal and adult hematopoietic stem cell regulation

“…Previous studies had shown CD44 is highly expressed on adult HSC 57 and early erythroid progenitors, but down-regulated during lineage commitment. 24 In addition, adult BM cells with colony-forming-unit granulocytes-macrophage and burst-forming unit-erythroid are H. Cao et al 32 haematologica | 2016; 101(1) Figure 6.…”

Not just a marker: CD34 on human hematopoietic stem/progenitor cells dominates vascular selectin binding along with CD44

“…24,25 BM transplantation studies into lethally irradiated mice lacking both endothelial selectins revealed that these mice exhibited a substantial defect in HSPC homing and a reduced survival that was rescued following the expression of either E-or P-selectin. 26 These and several other independent lines of evidence have highlighted vascular-selectindependent interactions as central to the recruitment of HSPC to BM. [26][27][28][29] In the current study, we determine the link between CD34 expression and the concurrent hematopoietic activation that leads to its improved homing and whether these vascular selectins can explain the gap in our understanding of this process.…”

“…26 These and several other independent lines of evidence have highlighted vascular-selectindependent interactions as central to the recruitment of HSPC to BM. [26][27][28][29] In the current study, we determine the link between CD34 expression and the concurrent hematopoietic activation that leads to its improved homing and whether these vascular selectins can explain the gap in our understanding of this process. We revealed a more defined role for CD34 as a vascular selectin ligand and showed that it has comparable affinity and functional performance to other selectin ligands on human HSPCs.…”

Myelomonocytic Cell Lines in Modeling HIV-1 Infection of the Bone Marrow

“…hematopoietic cells [24]. The CD34 sialomucin receptor is one of the several adhesions involved in the intra and extramedullary homing of progenitor cells into distinct microenvironments [25,26].…”