Abstract
Mesenchymal stromal cells are an important component of the bone marrow microenvironment (niche), where they support hematopoiesis via direct cell‑cell interactions with hematopoietic stem and progenitor cells, and by releasing soluble factors. Glycans, including N‑glycans, are involved in numerous biological processes, including inflammation, cell‑cell interactions, as well as cancer development and progression. Lectin‑based microarray analysis has provided a powerful new tool in recent years, for the investigation of aberrantly expressed N‑glycans and their functions in the bone marrow microenvironment. In the present study, we used an in vitro stromal/hematopoietic cell co‑culture system to examine the effects of stromal‑derived signals on apoptosis susceptibility of co‑cultured KG1a hematopoietic cells under hypoxic (1% O2) conditions. MALDI‑TOF/TOF‑MS analysis was used for the comparative global profiling of N‑glycans in KG1a cells and co‑cultured KG1a cells under hypoxia. KG1a cells became more susceptible to p53‑dependent apoptosis when co‑cultured with HS27A human stromal cells (derived from normal bone marrow) under hypoxia. We observed enhanced levels of core‑fucosylated N‑glycans (catalyzed by FUT8), bisecting GlcNAc (catalyzed by MGAT3), and their corresponding genes in co‑cultured cells. In addition we observed that overexpressing MGAT3 or FUT8 facilitated cell apoptosis in KG1a cells. Collectively, our data revealed the profiling of N‑glycans in KG1a cells before and after stroma contact. Our findings and future functional studies of core‑fucosylated N‑glycans and bisecting GlcNAc, will improve our understanding of the bone marrow microenvironment.