Környei Zsuzsanna, Szlávik Vanda, Szabó Bálint, Gócza Elen, Czirók András, Madarász Emília
Institute of Experimental Medicine, Hungarian Academy of Sciences, P.O. Box 67, H-1450 Budapest, Hungary.
Glia. 2005 Feb;49(3):430-44. doi: 10.1002/glia.20123.
Astroglial cells support or restrict the migration and differentiation of neural stem cells depending on the developmental stage of the progenitors and the physiological state of the astrocytes. In the present study, we show that astroglial cells instruct noncommitted, immortalized neuroectodermal stem cells to adopt a neuronal fate, while they fail to induce neuronal differentiation of embryonic stem cells under similar culture conditions. Astrocytes induce neuron formation by neuroectodermal progenitors both through direct cell-to-cell contacts and via short-range acting humoral factors. Neuron formation takes place inside compact stem cell assemblies formed 30- 60 h after the onset of glial induction. Statistical analyses of time-lapse microscopic recordings show that direct contacts with astrocytes hinder the migration of neuroectodermal progenitors, while astroglia-derived humoral factors increase their motility. In non-contact co-cultures with astrocytes, altered adhesiveness prevents the separation of frequently colliding neural stem cells. By contrast, in contact co-cultures with astrocytes, the restricted migration on glial surfaces keeps the cell progenies together, resulting in the formation of clonally proliferating stem cell aggregates. The data indicate that in vitro maintained parenchymal astrocytes (1) secrete factors, which initiate neuronal differentiation of neuroectodermal stem cells; and (2) provide a cellular microenvironment where stem cell/stem cell interactions can develop and the sorting out of the future neurons can proceed. In contrast to noncommitted progenitors, postmitotic neuronal precursors leave the stem cell clusters, indicating that astroglial cells selectively support the migration of maturing neurons as well as the elongation of neurites.
星形胶质细胞根据祖细胞的发育阶段和星形胶质细胞的生理状态，支持或限制神经干细胞的迁移和分化。在本研究中，我们发现星形胶质细胞可指导未分化的永生化神经外胚层干细胞转变为神经元命运，而在相似培养条件下，它们无法诱导胚胎干细胞向神经元分化。星形胶质细胞通过直接的细胞间接触和短程作用的体液因子，诱导神经外胚层祖细胞形成神经元。神经元形成发生在胶质诱导开始后30 - 60小时形成的紧密干细胞聚集体内。延时显微镜记录的统计分析表明，与星形胶质细胞的直接接触会阻碍神经外胚层祖细胞的迁移，而星形胶质细胞衍生的体液因子会增加其运动性。在与星形胶质细胞的非接触共培养中，黏附性的改变会阻止频繁碰撞的神经干细胞分离。相比之下，在与星形胶质细胞的接触共培养中，在胶质表面受限的迁移使细胞后代聚集在一起，导致形成克隆增殖的干细胞聚集体。数据表明，体外培养的实质星形胶质细胞(1)分泌启动神经外胚层干细胞神经元分化的因子；(2)提供一个细胞微环境，使干细胞/干细胞间相互作用得以发展，未来神经元得以分选。与未分化的祖细胞不同，有丝分裂后的神经元前体离开干细胞簇，这表明星形胶质细胞选择性地支持成熟神经元的迁移以及神经突的延伸。
