Differential Regulation of CXCL5 by FGF2 in Osteoblastic and Endothelial Niche Cells Supports Hematopoietic Stem Cell Migration

Abstract

Stem cell maintenance requires a specific microenvironment. Hematopoietic stem cells (HSCs) are mainly maintained by the endosteal osteoblast (OB) niche, which provides a quiescent HSC microenvironment, and the vascular niche, which regulates the proliferation, differentiation, and mobilization of HSCs. The systemic administration of FGF2 failed to induce normal hematopoiesis in bone marrow (BM) by reducing SDF-1, an important factor for hematopoiesis. Interestingly, SDF-1 levels were decreased in the OBs, but increased in vascular endothelial C166 cells when FGF2 was administered. We hypothesized that FGF2 induces changes in HSC migration from BM; therefore, we investigated FGF2-induced factors of HSC migration by a microarray chip. We searched the genes that were decreased in primary OBs, but increased in C166 cells upon FGF2 treatment. We confirmed selected genes that function in the extracellular region and identified the CXCR2-related chemokine candidate LIX/Cxcl5. A chemotaxis assay showed that CXCL5 induced the migration of HSCs (CD34(-/low)LSK). Our data suggest that the differential regulation of the chemokine CXCL5 between OBs and endothelial cells upon FGF2 treatment is involved in HSC mobilization from the OB niche or BM to peripheral blood.