Hart I K, Richardson W D, Heldin C H, Westermark B, Raff M C
MRC Developmental Neurobiology Programme, University College London, UK.
Development. 1989 Mar;105(3):595-603. doi: 10.1242/dev.105.3.595.
It has been shown previously that cultures of rat optic nerve contain three types of macroglial cells--oligodendrocytes and two types of astrocytes. Type-1 astrocytes develop from their own precursor cells beginning before birth, while oligodendrocytes and type-2 astrocytes develop postnatally from a common bipotential precursor called the O-2A progenitor cell. Proliferating O-2A progenitor cells give rise to postmitotic oligodendrocytes beginning around birth, and to type-2 astrocytes beginning in the second postnatal week. Studies in vitro have suggested that platelet-derived growth factor (PDGF), secreted by type-1 astrocytes, plays an important part in timing oligodendrocyte development: PDGF seems to keep O-2A progenitor cells proliferating until an intrinsic clock in the progenitor cells initiates the process leading to oligodendrocyte differentiation. The clock apparently determines when a progenitor cell becomes unresponsive to PDGF, at which point the cell stops dividing and, as a consequence, automatically differentiates into an oligodendrocyte. Here we have used radiolabelled PDGF to show that O-2A progenitor cells have PDGF receptors, suggesting that these cells respond directly to PDGF. The receptors resemble the type A PDGF receptor previously described on human fibroblasts and are initially retained when progenitor cells stop dividing and develop in vitro into oligodendrocytes. The latter finding indicates that receptor loss is not the reason that progenitor cells initially become mitotically unresponsive to PDGF.
先前的研究表明，大鼠视神经培养物中含有三种类型的大胶质细胞——少突胶质细胞和两种类型的星形胶质细胞。1型星形胶质细胞从出生前就开始由其自身的前体细胞发育而来，而少突胶质细胞和2型星形胶质细胞在出生后由一种称为O-2A祖细胞的共同双能前体细胞发育而来。增殖的O-2A祖细胞在出生前后开始产生有丝分裂后的少突胶质细胞，在出生后第二周开始产生2型星形胶质细胞。体外研究表明，1型星形胶质细胞分泌的血小板衍生生长因子（PDGF）在少突胶质细胞发育的时间调控中起重要作用：PDGF似乎使O-2A祖细胞持续增殖，直到祖细胞内的一个内在时钟启动导致少突胶质细胞分化的过程。这个时钟显然决定了祖细胞何时对PDGF不再有反应，此时细胞停止分裂，进而自动分化为少突胶质细胞。在这里，我们使用放射性标记的PDGF来表明O-2A祖细胞具有PDGF受体，这表明这些细胞直接对PDGF作出反应。这些受体类似于先前在人成纤维细胞上描述的A型PDGF受体，并且当祖细胞停止分裂并在体外发育为少突胶质细胞时，这些受体最初会保留下来。后一个发现表明，受体丧失并不是祖细胞最初对PDGF产生有丝分裂无反应的原因。
