Instituto do Cérebro, Universidade Federal do Rio Grande do Norte, 59072-970 Natal, Brazil.
Development. 2011 Mar;138(6):1057-68. doi: 10.1242/dev.061663.
Little is known about the intrinsic specification of adult neural stem cells (NSCs) and to what extent they depend on their local niche. To observe adult NSC division and lineage progression independent of their niche, we isolated cells from the adult mouse subependymal zone (SEZ) and cultured them at low density without growth factors. We demonstrate here that SEZ cells in this culture system are primarily neurogenic and that adult NSCs progress through stereotypic lineage trees consisting of asymmetric stem cell divisions, symmetric transit-amplifying divisions and final symmetric neurogenic divisions. Stem cells, identified by their astro/radial glial identity and their slow-dividing nature, were observed to generate asymmetrically and fast-dividing cells that maintained an astro/radial glia identity. These, in turn, gave rise to symmetrically and fast-dividing cells that lost glial hallmarks, but had not yet acquired neuronal features. The number of amplifying divisions was limited to a maximum of five in this system. Moreover, we found that cell growth correlated with the number of subsequent divisions of SEZ cells, with slow-dividing astro/radial glia exhibiting the most substantial growth prior to division. The fact that in the absence both of exogenously supplied growth factors and of signals provided by the local niche neurogenic lineage progression takes place in such stereotypic fashion, suggests that lineage progression is, to a significant degree, cell intrinsic or pre-programmed at the beginning of the lineage.
关于成年神经干细胞（NSCs）的内在特性以及它们在多大程度上依赖于其局部生态位，人们知之甚少。为了观察成年 NSCs 的分裂和谱系进展，而不依赖于其生态位，我们从成年小鼠室管膜下区（SEZ）中分离细胞，并在没有生长因子的低浓度条件下培养它们。在这里，我们证明了在这种培养系统中，SEZ 细胞主要具有神经发生能力，并且成年 NSCs 通过由不对称干细胞分裂、对称过渡扩增分裂和最终对称神经发生分裂组成的典型谱系树进行发育。通过其星形/放射状胶质细胞身份和缓慢分裂的特性鉴定出干细胞，观察到它们进行不对称和快速分裂，产生维持星形/放射状胶质细胞身份的细胞。这些细胞反过来又产生了失去神经胶质特征但尚未获得神经元特征的对称和快速分裂的细胞。在这个系统中，扩增分裂的数量最多限制为五次。此外，我们发现细胞生长与 SEZ 细胞随后分裂的数量相关，在分裂之前，缓慢分裂的星形/放射状胶质细胞表现出最大的生长。事实上，在没有外源生长因子和局部生态位提供的信号的情况下，神经发生谱系以如此典型的方式进行，这表明谱系进展在很大程度上是细胞内在的或在谱系开始时预先编程的。
