A supporting environment for hematopoietic stem/progenitor cells is maintained by canonical Wnt signaling

Considerable information has accumulated about components of bone marrow that regulate survival, self-renewal and differentiation of hematopoietic cells. We have now studied Wnt signaling in that context, assessing influences on human and murine hematopoiesis. Microarray, PCR and staining experiments revealed that OP9 acquired osteoblastic characteristics while down-regulating some features associated with mesenchymal stem cells. This included down-regulation of Angiopoietin 1, c-Kit ligand and VCAM-1 expression. In contrast, production of decorin, tenascins and fibromodulin markedly increased. At least one of these extracellular matrix components, decorin is a regulator of hematopoiesis. That is, addition of the protein to OP9 co-cultures causes changes similar to Wnt3a. Two control samples (LZR1 & LZR2) were analyzed from OP9 mouse stromal cells transfected with vector only, and two experimental samples (W3A1 & W3A2) were analyzed from OP9 cells transfected with vector containing the Wnt3A gene.