Institute of Molecular Regenerative Medicine, Paracelsus Medical University Salzburg, Strubergasse 21, Salzburg 5020, Austria.
Stem Cell Rev Rep. 2011 Nov;7(4):815-35. doi: 10.1007/s12015-011-9251-9.
It is commonly accepted that adult neurogenesis and gliogenesis follow the same principles through the mammalian class. However, it has been reported that neurogenesis might differ between species, even from the same order, like in rodents. Currently, it is not known if neural stem/progenitor cells (NSPCs) from various species differ in their cell identity and potential. NSPCs can be expanded ex vivo as neurospheres (NSph), a model widely used to study neurogenesis in vitro. Here we demonstrate that rat (r) and mouse (m) NSph display different cell identities, differentiation fate, electrophysiological function and tumorigenic potential. Adult rNSph consist mainly of oligodendroglial progenitors (OPCs), which after repeated passaging proliferate independent of mitogens, whereas adult mNSph show astroglial precursor-like characteristics and retain their mitogen dependency. Most of the cells in rNSph express OPC markers and spontaneously differentiate into oligodendrocytes after growth factor withdrawal. Electrophysiological analysis confirmed OPC characteristics. mNSph have different electrophysiological properties, they express astrocyte precursor markers and spontaneously differentiate primarily into astrocytes. Furthermore, rNSph have the potential to differentiate into oligodendrocytes and astrocytes, whereas mNSph are restricted to the astrocytic lineage. The phenotypic differences between rNSph and mNSph were not due to a distinct response to species specific derived growth factors and are probably not caused by autocrine mechanisms. Our findings suggest that NSph derived from adult rat and mouse brains display different cell identities. Thus, results urge for caution when data derived from NSph are extrapolated to other species or to the in vivo situation, especially when aimed towards the clinical use of human NSph.
普遍认为，在哺乳动物纲中，成神经发生和神经胶质发生遵循相同的原则。然而，据报道，神经发生可能因物种而异，即使是同一目，如在啮齿动物中。目前，尚不清楚来自不同物种的神经干细胞/祖细胞（NSPCs）在其细胞身份和潜能上是否存在差异。NSPCs 可以在体外作为神经球（NSph）进行扩增，这是一种广泛用于研究体外神经发生的模型。在这里，我们证明大鼠（r）和小鼠（m）NSph 显示出不同的细胞身份、分化命运、电生理功能和致瘤潜能。成年 rNSph 主要由少突胶质前体细胞（OPCs）组成，这些细胞在反复传代后可以在没有有丝分裂原的情况下增殖，而成年 mNSph 则表现出星形胶质前体细胞样特征，并保留其有丝分裂原依赖性。rNSph 中的大多数细胞表达 OPC 标志物，并在生长因子耗尽后自发分化为少突胶质细胞。电生理分析证实了 OPC 的特征。mNSph 具有不同的电生理特性，它们表达星形胶质前体细胞标志物，并自发分化为主要为星形胶质细胞。此外，rNSph 有分化为少突胶质细胞和星形胶质细胞的潜力，而 mNSph 则局限于星形胶质细胞谱系。rNSph 和 mNSph 之间的表型差异不是由于对物种特异性衍生生长因子的不同反应引起的，也可能不是由自分泌机制引起的。我们的研究结果表明，来自成年大鼠和小鼠大脑的 NSph 显示出不同的细胞身份。因此，当从 NSph 获得的数据外推到其他物种或体内情况时，特别是当旨在将人类 NSph 用于临床应用时，结果需要谨慎。
