Remodeling of Marrow Hematopoietic Stem and Progenitor Cells by Non-self ST6Gal-1 Sialyltransferase

Abstract

Background: The circulatory ST6Gal-1 level is inversely related to hematopoietic activity, but the biochemical function of systemic ST6Gal-1 is unknown. Results: Hematopoietic progenitors do not express self-ST6Gal-1 but are acted upon by remotely produced enzyme. Conclusion: Distally produced rather than endogenous ST6Gal-1 is the principal modifier of the early hematopoietic progenitor cell surface. Significance: Extrinsic ST6Gal-1 may be a potent systemic regulator of hematopoiesis.

Platelets Support Extracellular Sialylation by Supplying the Sugar Donor Substrate

“…In a separate study, we showed that the surface ␣2,6-sialyl structures of hematopoietic progenitor cells were generated exclusively by extrinsic ST6Gal-1 rather than the endogenously expressed enzyme, and the action of the extrinsic sialyltransferase resulted in hematopoietic arrest (15). Here, we demonstrate that activated platelets can functionally support extrinsic ST6Gal-1 sialylation of hematopoietic progenitor cells.…”

“…Glycans occupy the critical interface between each cell and its outside environment. Extrinsic glyco- syltransferases, such as the circulatory ST6Gal-1, can alter cell behavior by remodeling the glycan interface (15). Because circulatory ST6Gal-1 is freely available, platelets may serve as a pivotal moderator of glycosylation by controlling the release of the necessary substrates.…”

“…Recently, we obtained definitive evidence that the ␣2,6-sialyl structures on hematopoietic progenitor cell surfaces are constructed by the extracellular ST6Gal-1 in circulation, rather than the cell-autonomously expressed enzyme of the individual hematopoietic cells (15). In doing so, the circulatory ST6Gal-1 that principally originates from liver acts as a systemic regulator of hematopoiesis by delaying hematopoietic progenitor proliferation and differentiation.…”

“…LK cells were isolated from lineage-depleted pools using anti-cKit (CD117) microbeads (STEMCELL Technologies for LK cells). Soluble ST6Gal-1 used throughout this study was produced as described elsewhere (15).…”

Post-conversion sialylation of prions in lymphoid tissues

“…Traditionally, STs were thought to localize exclusively within the intracellular secretory apparatus (50). A growing number of studies report ST activity in serum or on surfaces of the cells of immune system, including polymorphonuclear leukocyte, monocyte-derived dendritic cells, lymphocytes, and T cells (48,49,(51)(52)(53)80). Presence of ST on the cell surface or in serum allows rapid restoration or remodeling of the sialylation status of cells without de novo synthesis of cell surface glycoconjugates (48,49,81).…”