Distribution of CD133 reveals glioma stem cells self-renew through symmetric and asymmetric cell divisions.
Distribution of CD133 reveals glioma stem cells self-renew through symmetric and asymmetric cell divisions.
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DOI：
10.1038/cddis.2011.80
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发表时间：
2011-09-01
影响因子：
9
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中科院分区：
文献类型：
--
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恶性胶质瘤含有一群自我更新的致瘤干细胞样细胞;然而，目前仍不清楚这些胶质瘤干细胞（GSC）如何自我更新或在单细胞水平上产生细胞多样性。不对称细胞分裂是维持癌症干细胞的一种拟议机制，但GSC利用的细胞分裂模式仍不确定。在这里，我们使用单细胞分析来评估GSC的细胞分裂行为。谱系追踪分析表明，大多数GSC是通过扩张性对称细胞分裂而不是通过不对称细胞分裂产生的。大多数分化的后代是通过在扩增条件下的对称亲定型分裂产生的，并且在不存在生长因子的情况下，主要通过不对称细胞分裂发生。有丝分裂对分析检测到不对称的CD 133分离，而不是任何其他GSC标记的一部分有丝分裂，其中一些与Numb不对称。在生长因子戒断条件下，不对称CD 133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增加一致。使用基于单细胞的观察，我们提供了明确的证据，GSC能够不同的细胞分裂模式，细胞多样性的产生主要通过对称细胞分裂发生，而不是通过不对称细胞分裂。
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.
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