Figure 9.

Working model describing the changes in the bone marrow microenvironment in VhlcKO mice. Left panel: Schematic of healthy control bone marrow where VHL/HIF signaling is intact, the transition from osteoblasts to osteocytes is homeostatically balanced and interactions of developing B cells and stromal cells within their niches promotes their differentiation, maturation and proliferation. Right panel: Lack of Vhl in late osteoblasts and osteocytes has a severe effect on hematopoiesis in the bone marrow, changing the B cell niche and indirectly regulating B cell development through decrease of CXCL12, increase of EPO and changes to the BM microenvironment vasculature and permeability. Changes in the oxygen levels in the local niches for Fraction A cells do not occur until later ages, as shown by pimonidazole staining. Direct measurement of pO₂ in the BM is necessary to determine if the BM oxygenation landscape is altered compared to controls.