DNA microarray analysis of differential gene expression of 6-year-old rat neural striatal progenitor cells during early differentiation

EGF-responsive striatal progenitor cells from rat brain have been maintaine d in culture in the form of neurospheres for six years without exhausting t heir renewal capacity. The events surrounding differentiation of stem cells in the brain after a long progenitorship remain a mystery. Using DNA micro array analysis we investigated differential gene expression, comparing prog enitor cells in their neurosphere state with the cells 24 hours after induc tion of differentiation. Eighty-one genes showed increased expression in th e differentiated condition. Genes associated with cellular growth, neurite outgrowth, and synaptogenesis were activated, including both anti-apoptotic and pro-apoptotic genes. Two transmitter-related genes, acetylcholine rece ptor-P and glutamate receptor-p-unit were also elevated; these genes not on ly fit the profile of early neural development, but also reflect the charac teristics of striatal neurons. In addition, there are approximately 30 expr essed sequence tags (EST) increased during neural differentiation. Forty-se ven genes showed decreased expression; half of them are known genes related to the cell cycle, cell adhesion, transcription, and signaling. The signal ing and cell cycle genes may be responsible for the life-long self-renewal. These data demonstrate for the first time that life-long quiescent stem ce lls retain the potential to become activated and develop into specific type s of brain cells. The six-year long-term neural stem cells are an excellent model for studying developmental neurobiological processes and aging.