Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Cell Death Dis. 2011 Sep 1;2(9):e200. doi: 10.1038/cddis.2011.80.
Malignant gliomas contain a population of self-renewing tumorigenic stem-like cells; however, it remains unclear how these glioma stem cells (GSCs) self-renew or generate cellular diversity at the single-cell level. Asymmetric cell division is a proposed mechanism to maintain cancer stem cells, yet the modes of cell division that GSCs utilize remain undetermined. Here, we used single-cell analyses to evaluate the cell division behavior of GSCs. Lineage-tracing analysis revealed that the majority of GSCs were generated through expansive symmetric cell division and not through asymmetric cell division. The majority of differentiated progeny was generated through symmetric pro-commitment divisions under expansion conditions and in the absence of growth factors, occurred mainly through asymmetric cell divisions. Mitotic pair analysis detected asymmetric CD133 segregation and not any other GSC marker in a fraction of mitoses, some of which were associated with Numb asymmetry. Under growth factor withdrawal conditions, the proportion of asymmetric CD133 divisions increased, congruent with the increase in asymmetric cell divisions observed in the lineage-tracing studies. Using single-cell-based observation, we provide definitive evidence that GSCs are capable of different modes of cell division and that the generation of cellular diversity occurs mainly through symmetric cell division, not through asymmetric cell division.
恶性神经胶质瘤中存在一群自我更新的肿瘤起始干细胞样细胞；然而，这些神经胶质瘤干细胞（GSCs）如何在单细胞水平上自我更新或产生细胞多样性仍不清楚。不对称细胞分裂是维持癌症干细胞的一种提出的机制，但 GSCs 利用的细胞分裂模式仍未确定。在这里，我们使用单细胞分析来评估 GSCs 的细胞分裂行为。谱系追踪分析表明，大多数 GSCs 是通过扩张性对称细胞分裂产生的，而不是通过不对称细胞分裂产生的。大多数分化后代是在扩张条件下和没有生长因子的情况下通过对称的前承诺分裂产生的，主要通过不对称细胞分裂产生。有丝分裂对分析检测到在有丝分裂的一小部分中，不对称的 CD133 分离，而不是任何其他 GSC 标记，其中一些与 Numb 不对称有关。在生长因子撤出条件下，不对称 CD133 分裂的比例增加，与谱系追踪研究中观察到的不对称细胞分裂的增加一致。通过基于单细胞的观察，我们提供了明确的证据，证明 GSCs 能够进行不同的细胞分裂模式，并且细胞多样性的产生主要通过对称细胞分裂，而不是通过不对称细胞分裂。
