Doetsch F, Caillé I, Lim D A, García-Verdugo J M, Alvarez-Buylla A
The Rockefeller University, New York, New York 10021, USA.
Cell. 1999 Jun 11;97(6):703-16. doi: 10.1016/s0092-8674(00)80783-7.
Neural stem cells reside in the subventricular zone (SVZ) of the adult mammalian brain. This germinal region, which continually generates new neurons destined for the olfactory bulb, is composed of four cell types: migrating neuroblasts, immature precursors, astrocytes, and ependymal cells. Here we show that SVZ astrocytes, and not ependymal cells, remain labeled with proliferation markers after long survivals in adult mice. After elimination of immature precursors and neuroblasts by an antimitotic treatment, SVZ astrocytes divide to generate immature precursors and neuroblasts. Furthermore, in untreated mice, SVZ astrocytes specifically infected with a retrovirus give rise to new neurons in the olfactory bulb. Finally, we show that SVZ astrocytes give rise to cells that grow into multipotent neurospheres in vitro. We conclude that SVZ astrocytes act as neural stem cells in both the normal and regenerating brain.
神经干细胞存在于成年哺乳动物大脑的脑室下区(SVZ)。这个不断产生注定要进入嗅球的新神经元的生发区域由四种细胞类型组成:迁移的神经母细胞、未成熟前体细胞、星形胶质细胞和室管膜细胞。我们在此表明,在成年小鼠长期存活后,SVZ星形胶质细胞而非室管膜细胞仍带有增殖标记。在用抗有丝分裂处理消除未成熟前体细胞和神经母细胞后,SVZ星形胶质细胞分裂产生未成熟前体细胞和神经母细胞。此外,在未处理的小鼠中,经逆转录病毒特异性感染的SVZ星形胶质细胞在嗅球中产生新的神经元。最后,我们表明SVZ星形胶质细胞产生的细胞在体外可生长为多能神经球。我们得出结论,SVZ星形胶质细胞在正常大脑和再生大脑中均充当神经干细胞。