Distinct Effects of Chondroitin Sulfate on Hematopoietic Cells and Stromal Microenvironment in Bone Marrow Hematopoiesis. Mus musculus

Chondroitin sulfate (CS) is a kind of glycosaminoglycans (GAGs), which are long linear polysaccharides of repetitive disaccharide sequences comprised of an amino sugar. CS N-acetylgalactosaminyltransferase-1 (CsGalNAcT1) is the key enzyme for CS production. The CSGalNAcT1 dependent pathway cannot be compensated for by other enzymes, thus is assumed to be important for regulating CS levels. Correspondingly, the amount of CS disaccharides bone marrow (BM) were reduced in CSGalNAcT1 KO (T1KO) mic approximately two-thirds of that in wild-type (WT) mice. Although CsGalNAcT1 loss did not have any significant effects on hematopoiesis in a steady state, hematopoietic stem and progenitor cells (HSPCs) from T1KO mice showed moderately but significantly impaired repopulation in WT recipient mice upon serial transplantations. In contrast, numbers of WT HSPCs repopulated in T1KO recipient mice were higher than those in WT recipient mice during serial transplantations, indicating that T1KO BM niche supports repopulation of HSPCs better than WT BM niche. RNA sequence analysis revealed that the loss of CsGalNAcT1 in HSPCs is associated with activation of IFN-a/b signal and endoplasmic reticulum (ER) stress. Our results unveiled the contradictory effects of CS on hematopoietic cells and BM niche. Crosstalk between these pathways is considered to be important in hematopoiesis. Manipulating the amount of CS in HSPCs and BM niche may improve clinical hematopoietic stem cell transplantation outcome.