irradiationinduced secretion of bmp4 by marrow cells causes marrow adipogenesis postmyelosuppression pretransplant myeloablation is associated with marrow adipogenesis resulting in delayed engraftment of hematopoietic stem cells hscs this is strongly undesirable especially when the donor hscs are fewer in numbers or have compromised functionality the molecular mechanisms behind irradiationinduced marrow adipogenesis have not been extensively investigated here we show that bone marrow bm cells especially tcells and stromal cells express and secrete copious amounts of bmp4 in response to irradiation which causes the bone marrow stromal cells to commit to adipocyte lineage thereby contributing to an increase in bone marrow adipogenesis we further demonstrate that simvastatin inhibits the bmp4mediated adipogenic commitment of marrow stromal cells by inhibiting ppar expression importantly simvastatin does not prevent bmp4 secretion by the bm cells and thus does not interfere with its salutary role in posttransplant hematopoietic regeneration our data identify previously unknown mechanisms operative in marrow adipogenesis postmyeloablation they also reveal the molecular mechanisms behind the advantage of using simvastatin as a nichetargeting agent to improve hsc engraftment