HEMATOPOIETIC-CELLS DIFFERENTIATE INTO BOTH MICROGLIA AND MACROGLIA IN THE BRAINS OF ADULT MICE

Glial cells are thought to derive embryologically from either myeloid cells of the hematopoietic system (microglia) or neuroepithelial proge nitor cells (astroglia and oligodendrocytes). How ever, it is unclear whether the glia in adult brains free of disease or injury originate s olely from cells present in the brain since the fetal stage of develop ment, or if there is further input into such adult brains from cells o riginating outside the central nervous system. To test the ability of hematopoietic cells to contribute to the central nervous system, we ha ve transplanted adult female mice with donor bone marrow cells genetic ally marked either with a retroviral tag or by using male donor cells. Using in situ hybridization histochemistry, a continuing influx of he matopoietic cells into the brain was detected. Marrow-derived cells we re already detected in the brains of mice 3 days after transplant, and their numbers increased over the next several weeks, exceeding 14,000 cells per brain in several animals. Marrow-derived cells were widely distributed throughout the brain, including the cortex, hippocampus, t halamus, brain stem, and cerebellum. When in situ hybridization histoc hemistry was combined with immunohistochemical staining using lineage- specific markers, some bone marrow derived cells were positive for the microglial antigenic marker F4/80. Other marrow-derived cells surpris ingly expressed the astroglial marker glial fibrillary acidic protein. These results indicate that some microglia and astroglia arise from a precursor that is a normal constituent of adult bone marrow.