Mi H, Haeberle H, Barres B A
Stanford University School of Medicine, Department of Neurobiology, Stanford, California 94305-5125, USA.
J Neurosci. 2001 Mar 1;21(5):1538-47. doi: 10.1523/JNEUROSCI.21-05-01538.2001.
Here we have investigated the mechanisms that control astrocyte differentiation within the developing rat optic nerve. Astrocytes are normally generated by astrocyte precursor cells within the embryonic optic nerve. We show that there is a close temporal and spatial correlation between endothelial and astrocyte differentiation. We tested the potential role of endothelial cells in inducing astrocyte differentiation by developing an immunopanning method to highly purify endothelial cells from developing optic nerves. We show that the purified endothelial cells, but not other embryonic optic nerve cell types, strongly induce the differentiation of purified astrocyte precursor cells into astrocytes in vitro. Leukemia inhibitory factor (LIF) and LIF receptors have been implicated previously in astrocyte differentiation in vivo. We show that purified endothelial cells express LIF mRNA and that their ability to induce astrocyte differentiation is prevented by a neutralizing anti-LIF, but not anti-ciliary neurotrophic factor, antiserum. These findings demonstrate a role for endothelial cells in inducing astrocyte differentiation. The induction of astrocyte differentiation by endothelial cells makes sense phylogenetically, anatomically, and functionally, because astrocytes evolved concurrently with brain vasculature and ensheathe capillaries throughout the brain. The ability to purify and culture astrocytes and endothelial cells should provide an excellent model system for future studies of blood-brain barrier development.
在此，我们研究了发育中的大鼠视神经内控制星形胶质细胞分化的机制。星形胶质细胞通常由胚胎视神经内的星形胶质细胞前体细胞产生。我们发现内皮细胞和星形胶质细胞的分化在时间和空间上存在密切关联。我们通过开发一种免疫淘选方法，从发育中的视神经中高度纯化内皮细胞，来测试内皮细胞在诱导星形胶质细胞分化中的潜在作用。我们发现，纯化的内皮细胞，而非其他胚胎视神经细胞类型，能在体外强烈诱导纯化的星形胶质细胞前体细胞分化为星形胶质细胞。白血病抑制因子（LIF）及其受体先前已被认为与体内星形胶质细胞分化有关。我们发现纯化的内皮细胞表达LIF mRNA，并且其诱导星形胶质细胞分化的能力可被中和性抗LIF抗体而非抗睫状神经营养因子抗血清所阻断。这些发现证明了内皮细胞在诱导星形胶质细胞分化中的作用。从系统发育、解剖学和功能角度来看，内皮细胞诱导星形胶质细胞分化是合理的，因为星形胶质细胞与脑血管系统同时进化，并包裹着整个大脑的毛细血管。纯化和培养星形胶质细胞及内皮细胞的能力应为未来血脑屏障发育研究提供一个出色的模型系统。
