Vitamin D receptor deletion leads to increased hematopoietic stem and progenitor cells residing in the spleen

Abstract

Bone components participate in the regulation of hematopoietic stem cells in the adult mammal. Vitamin D regulates bone mineralization and is associated with pleiotropic effects in many cell types, including putative roles in hematopoietic differentiation. We report that deletion of the vitamin D receptor (VDR) in hematopoietic cells did not result in cell autonomous perturbation of hematopoietic stem cell or progenitor function. However, deletion of VDR in the microenvironment resulted in a marked accumulation of hematopoietic stem cells in the spleen that could be reversed by calcium dietary supplementation. These data suggest that VDR participates in restricting splenic hematopoiesis through maintenance of bone calcium homeostasis and are consistent with the concept that calcium regulation through VDR is a central participant in localizing adult hematopoiesis preferentially to bone marrow. © 2010 by The American Society of Hematology.