Advances in stem cell biology have steadily increased the possibilities for studying diseases and developing treatments. Cultured mouse and human neural stem cells (NSCs) have been invaluable for the investigation of neurodegenerative diseases and the screening of pharmacological compounds. Rats have been used extensively for cognitive, pharmaceutical and surgical research, so cultured rat NSCs would, therefore, be beneficial for complementary in vitro studies. Unfortunately, culturing rat NSCs has proven difficult so far, because they arrest proliferation and differentiate. In search for conditions that allow long-term maintenance of rat NSCs in vitro, Austin Smith and colleagues (page ) identify an extrinsic stimulatory network comprising bone morphogenetic protein (BMP) and fibroblast growth factor (FGF) 2 that regulates rat NSC proliferation and differentiation. They show that autocrine BMP stimulation induces growth arrest through members of the Smad family of transcription factors – an effect that can be overcome by conditioned medium from proliferating cells or the BMP antagonist Noggin. Importantly, FGF2 is necessary to block terminal differentiation in the presence of BMP and maintain potency in quiescent NSCs. It is thus the careful balance of these two factors that is required to regulate rat NSC cell fate; manipulating this balance in vitro provides a new way to achieve their long-term expansion.
