Remodeling of marrow hematopoietic stem and progenitor cells by non-self ST6Gal-1 sialyltransferase [Developmental Biology]

January 14th, 2014 by Nasirikenari, M., Veillon, L., Collins, C. C., Azadi, P., Lau, J. T. Y.

Glycans occupy the critical cell surface interface between hematopoietic cells and their marrow niches. Typically, glycosyltransferases reside within the intracellular secretory apparatus, and each cell generates autonomously its own cell surface glycans. In this study, we report an alternate pathway to generate cell surface glycans where remotely produced glycosyltransferases remodel surfaces of target cells, and does not require endogenous expression of the cognate enzymes. Our data show that extracellular ST6Gal-1 sialyltransferase, originating mostly from the liver and released into circulation, targets marrow hematopoietic stem and progenitor cells (HSPCs) and mediates the formation of cell surface [alpha]2,6-linked sialic acids on HSPCs, as assessed by binding to the specific lectins, SNA (Sambucus nigra) and PSL (Polysporus squamosus) and confirmed by mass spectrometry. Marrow HSPCs, operationally defined as the LK (LinnegcKitpos) and LSK (LinnegSca-1poscKitpos) populations, express negligible endogenous ST6Gal-1. Animals with reduced circulatory ST6Gal-1 have marrow LSK cells with reduced SNA reactivity. Bone marrow chimeras demonstrated that [alpha]2,6-sialylation of HSPCs is profoundly dependent on circulatory ST6Gal-1 status of the recipients, and independent of the HSPCs′ ability to express endogenous ST6Gal-1. Biologically, HSPC abundance in the marrow is inversely related to circulatory ST6Gal-1 status, and this relationship is recapitulated in the bone marrow chimeras. We propose that remotely produced, rather than the endogenously expressed ST6Gal-1, is the principal modifier of HSPC glycans for [alpha]2,6-sialic acids. In so doing, liver-produced ST6Gal-1 may be a potent systemic regulator of hematopoiesis.