Decellularized bone marrow reveals a novel niche protein that modulate adhesion

The hematopoietic marrow microenvironment is composed of multiple cell types embedded in an extracellular matrix (ECM). Decellurization of murine long bones was used to isolate ECM. The proteome signature was determined using mass spectrometry which identified over 240 proteins including Dermatopontin (DPT), a small non-collagenous ECM protein. To understand DPT’s role in the niche, we generated constitutional DPT-/- mice that were viable and had no peripheral lympho-hematopoietic abnormalities. Marrow composition of wild-type and DPT-/- mice was equivalent in terms of cellularity, CFU-C, LSK (Lineage-, SCA-1+, KIT+) and LSK-SLAM (LSK, CD48-, CD150+) frequencies. Interesting, when DPT-/- mice were used as recipients in adoptive transfer experiments, they displayed a 51% increase in donor cell homing 20 hours following lethal irradiation (n = 9 mice/group, p < 0.05); this translated to greater long term engraftment after primary and secondary transplants (sublethally irradiated, DPT-/- recipients engrafted at 60% vs 40% in wild-type (n = 12, p < 0.01). Conversely, pre-treating mice with recombinant DPT showed a 90% reduction (n = 12, p = 0.02) and a 40% reduction (n = 6, p < 0.05) in whole marrow and LSK cells that migrated to the marrow 20 hours post-transplant, respectively. This reduction in homing translated to decreases in short- and long-term multilineage engraftment. Furthermore, we also determined DPT can bind endothelial cells and DPT-/- mice displayed increased endothelial permeability. These data suggest that DPT plays a novel role in vascular integrity and cell adherence, but is not required for steady state hematopoiesis in vivo. As well, there are likely overlapping cellular adhesion mechanisms that can compensate to maintain the hematopoietic niche in the absence of DPT.