Shi J, Marinovich A, Barres B A
Stanford University School of Medicine, Department of Neurobiology, Stanford, California 94305-5125, USA.
J Neurosci. 1998 Jun 15;18(12):4627-36. doi: 10.1523/JNEUROSCI.18-12-04627.1998.
Oligodendrocyte precursor cells (OPCs) persist in substantial numbers in the adult brain in a quiescent state suggesting that they may provide a source of new oligodendrocytes after injury. To determine whether adult OPCs have the capacity to divide rapidly, we have developed a method to highly purify OPCs from adult optic nerve and have directly compared their properties with their perinatal counterparts. When cultured in platelet-derived growth factor (PDGF), an astrocyte-derived mitogen, perinatal OPCs divided approximately once per day, whereas adult OPCs divided only once every 3 or 4 d. The proliferation rate of adult OPCs was not increased by addition of fibroblast growth factor (FGF) or of the neuregulin glial growth factor 2 (GGF2), two mitogens that are normally produced by retinal ganglion cells. cAMP elevation has been shown previously to be essential for Schwann cells to survive and divide in response to GGF2 and other mitogens. Similarly we found that when cAMP levels were elevated, GGF2 alone was sufficient to induce perinatal OPCs to divide slowly, approximately once every 4 d, but adult OPCs still did not divide. When PDGF was combined with GGF2 and cAMP elevation, however, the adult OPCs began to divide rapidly. These findings indicate that adult OPCs are intrinsically different than perinatal OPCs. They are not senescent cells, however, because they retain the capacity to divide rapidly. Thus, after demyelinating injuries, enhanced axonal release of GGF2 or a related neuregulin might collaborate with astrocyte-derived PDGF to induce rapid division of adult OPCs.
少突胶质前体细胞（OPCs）大量静息存在于成体脑中，这表明它们可能在损伤后成为新的少突胶质细胞的来源。为了确定成体OPCs是否具有快速分裂的能力，我们开发了一种从成体视神经中高度纯化OPCs的方法，并直接将它们的特性与其围产期对应物进行比较。当在血小板衍生生长因子（PDGF，一种星形胶质细胞衍生的有丝分裂原）中培养时，围产期OPCs大约每天分裂一次，而成体OPCs每3或4天仅分裂一次。添加成纤维细胞生长因子（FGF）或神经调节蛋白胶质生长因子2（GGF2，两种通常由视网膜神经节细胞产生的有丝分裂原）并不能提高成体OPCs的增殖速率。先前已表明，cAMP升高对于雪旺细胞在响应GGF2和其他有丝分裂原时的存活和分裂至关重要。同样，我们发现，当cAMP水平升高时，单独的GGF2足以诱导围产期OPCs缓慢分裂，大约每4天一次，但成体OPCs仍然不分裂。然而，当PDGF与GGF2以及cAMP升高相结合时，成体OPCs开始快速分裂。这些发现表明，成体OPCs与围产期OPCs在本质上是不同的。然而，它们不是衰老细胞,因为它们保留了快速分裂的能力。因此，在脱髓鞘损伤后，GGF2或相关神经调节蛋白的轴突释放增强可能与星形胶质细胞衍生的PDGF协同作用，诱导成体OPCs快速分裂。
