Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor

Stem-cell guidance Haematopoietic stem cells ‘home’ to the bone marrow during embryogenesis and after bone marrow transplants. With the exception of integrins, the molecules that mediate this process are largely unknown. Now Adams et al . have identified another factor essential for homing, a membrane-spanning molecule called calcium-sensing receptor (CaR). Cells lacking CaR divide normally, but the newly formed cells are unable to migrate and home to the bone marrow. This newly recognized participant in the localization and engraftment of stem cells provides a potential target for affecting that process. During mammalian ontogeny, haematopoietic stem cells (HSCs) translocate from the fetal liver to the bone marrow, where haematopoiesis occurs throughout adulthood 1 . Unique features of bone that contribute to a microenvironmental niche for stem cells might include the known high concentration of calcium ions at the HSC-enriched endosteal surface. Cells respond to extracellular ionic calcium concentrations through the seven-transmembrane-spanning calcium-sensing receptor (CaR), which we identified as being expressed on HSCs. Here we show that, through the CaR, the simple ionic mineral content of the niche may dictate the preferential localization of adult mammalian haematopoiesis in bone. Antenatal mice deficient in CaR had primitive haematopoietic cells in the circulation and spleen, whereas few were found in bone marrow. CaR -/- HSCs from fetal liver were normal in number, in proliferative and differentiative function, and in migration and homing to the bone marrow. Yet they were highly defective in localizing anatomically to the endosteal niche, behaviour that correlated with defective adhesion to the extracellular matrix protein, collagen I. CaR has a function in retaining HSCs in close physical proximity to the endosteal surface and the regulatory niche components associated with it.