Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Cancer Cell. 2012 Jan 17;21(1):11-24. doi: 10.1016/j.ccr.2011.11.025.
Within high-grade gliomas, the precise identities and functional roles of stem-like cells remain unclear. In the normal neurogenic niche, ID (Inhibitor of DNA-binding) genes maintain self-renewal and multipotency of adult neural stem cells. Using PDGF- and KRAS-driven murine models of gliomagenesis, we show that high Id1 expression (Id1(high)) identifies tumor cells with high self-renewal capacity, while low Id1 expression (Id1(low)) identifies tumor cells with proliferative potential but limited self-renewal capacity. Surprisingly, Id1(low) cells generate tumors more rapidly and with higher penetrance than Id1(high) cells. Further, eliminating tumor cell self-renewal through deletion of Id1 has modest effects on animal survival, while knockdown of Olig2 within Id1(low) cells has a significant survival benefit, underscoring the importance of non-self-renewing lineages in disease progression.
在高级别神经胶质瘤中，干细胞样细胞的精确身份和功能角色仍不清楚。在正常的神经发生龛内，ID（DNA 结合抑制剂）基因维持成人神经干细胞的自我更新和多能性。使用 PDGF 和 KRAS 驱动的小鼠神经胶质瘤发生模型，我们表明高 Id1 表达（Id1(high)）鉴定出具有高自我更新能力的肿瘤细胞，而低 Id1 表达（Id1(low)）鉴定出具有增殖潜力但自我更新能力有限的肿瘤细胞。令人惊讶的是，Id1(low)细胞比 Id1(high)细胞更快且更易发生肿瘤。此外，通过删除 Id1 消除肿瘤细胞的自我更新对动物存活的影响不大，而在 Id1(low)细胞中敲低 Olig2 则具有显著的生存获益，这突显了非自我更新谱系在疾病进展中的重要性。
