Abstract
Although microglial cells are currently considered mesodermal cells, it has not been completely determined whether they are hematopoietic or mesenchymal origins. To obtain some insights in this issue, we induced dedifferentiation of microglial cells in culture by incubating in 70% serum-supplemented medium for 2 d. Microglial cells were separated from primary mixed glial culture that was started from neonatal rat forebrains or from ischemic brain lesions of rats whose right middle cerebral artery was transiently occluded. Cells cultured in 70% serum-medium gradually exhibited amoeboid shape and often formed cell aggregates, while increasing expression of Id genes and getting highly proliferative. Such cell aggregates differentiated into cells with neuroectodermal phenotypes after they were transferred into serum-free medium on poly-L-lysine-coated substrate. By contrast, cells that had been cultured in 70% serum-medium gradually fused resulting in formation of multinuclear giant cells, after they were transferred into 10% fetal calf serum-supplemented medium containing M-CSF and RANKL. As revealed by RT-PCR, such giant cells elevated expressions of mRNAs encoding DC-stamp, TRAP and Cathepsin K that are specific markers of osteoclasts. Taken that osteoclasts are derived from hematopoietic stem cells (HSCs) and HSCs are known to generate neuroectodermal cells, microglial cells may be of hematopoietic origin. [J Physiol Sci. 2006;56 Suppl:S121]