Khatri Priti, Obernier Kirsten, Simeonova Ina K, Hellwig Andrea, Hölzl-Wenig Gabriele, Mandl Claudia, Scholl Catharina, Wölfl Stefan, Winkler Johannes, Gaspar John A, Sachinidis Agapios, Ciccolini Francesca
Department of Neurobiology, Interdisciplinary Center for Neurosciences, University of Heidelberg, Heidelberg, Germany.
1] Department of Neurobiology, Interdisciplinary Center for Neurosciences, University of Heidelberg, Heidelberg, Germany [2].
Sci Rep. 2014 Jan 22;4:3803. doi: 10.1038/srep03803.
Neural stem cells (NSCs) generate new neurons in vivo and in vitro throughout adulthood and therefore are physiologically and clinically relevant. Unveiling the mechanisms regulating the lineage progression from NSCs to newborn neurons is critical for the transition from basic research to clinical application. However, the direct analysis of NSCs and their progeny is still elusive due to the problematic identification of the cells. We here describe the isolation of highly purified genetically unaltered NSCs and transit-amplifying precursors (TAPs) from the adult subependymal zone (SEZ). Using this approach we show that a primary cilium and high levels of epidermal growth factor receptor (EGFR) at the cell membrane characterize quiescent and cycling NSCs, respectively. However, we also observed non-ciliated quiescent NSCs and NSCs progressing into the cell cycle without up-regulating EGFR expression. Thus, the existence of NSCs displaying distinct molecular and structural conformations provides more flexibility to the regulation of quiescence and cell cycle progression.
神经干细胞(NSCs)在成年期的体内和体外均可产生新的神经元,因此在生理和临床上都具有重要意义。揭示调控神经干细胞向新生神经元谱系进展的机制对于从基础研究向临床应用的转变至关重要。然而,由于细胞识别存在问题,对神经干细胞及其子代的直接分析仍然难以实现。我们在此描述了从成年侧脑室下区(SEZ)分离高度纯化的基因未改变的神经干细胞和过渡放大前体细胞(TAPs)的方法。使用这种方法,我们发现初级纤毛和细胞膜上高水平的表皮生长因子受体(EGFR)分别表征静止和增殖的神经干细胞。然而,我们也观察到无纤毛的静止神经干细胞以及在未上调EGFR表达的情况下进入细胞周期的神经干细胞。因此,显示出不同分子和结构构象的神经干细胞的存在为静止和细胞周期进展的调控提供了更大的灵活性。