The Queensland Brain Institute, The University of Queensland, Brisbane QLD 4072, Australia.
Dev Neurobiol. 2011 Jul;71(7):619-33. doi: 10.1002/dneu.20871.
The regulation of neural precursor cell (NPC) activity is the major determinant of the rate of neuronal production in neurogenic regions of the adult brain. Here, we show that Oncostatin M (Osm) and its receptor, OsmRβ, are both expressed in the subventricular zone (SVZ) and that in contradistinction to leukemia inhibitory factor and ciliary neutrophic factor, Osm directly inhibits the proliferation of adult NPCs as measured by a decreased level of neurosphere formation in vitro. Similarly, intraventricular infusion of Osm dramatically decreases the pool of NPCs in both the SVZ and the hippocampus. In keeping with the inhibitory action of Osm, we reveal that mice lacking OsmRβ have substantially more NPCs in the SVZ, the hippocampus and the olfactory bulb, demonstrating that endogenous Osm signaling is important for NPC homeostasis. Finally, we show that Osm can also inhibit clonal growth of glioblastoma-derived neurospheres, further supporting the close link between NPCs and tumor stem cells.
神经前体细胞（NPC）活性的调节是成年大脑神经发生区域神经元产生速度的主要决定因素。在这里，我们表明，肿瘤坏死因子 M（Osm）及其受体 OsmRβ 均在侧脑室下区（SVZ）表达，与白血病抑制因子和睫状神经营养因子相反，Osm 通过体外神经球形成水平降低直接抑制成年 NPC 的增殖。同样，脑室内输注 Osm 可显著减少 SVZ 和海马体中 NPC 的数量。与 Osm 的抑制作用一致，我们揭示了缺乏 OsmRβ 的小鼠在 SVZ、海马体和嗅球中有更多的 NPC，表明内源性 Osm 信号对 NPC 稳态很重要。最后，我们还表明 Osm 还可以抑制神经球衍生的神经胶质瘤克隆的生长，这进一步支持了 NPC 和肿瘤干细胞之间的紧密联系。
