人类质母细胞的命运映射显示出不变的干细胞等级
Xiaoyang Lan1,2,3, David J Jörg4,5, Florence M G Cavalli1,2
1Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.
Nature
|August 31, 2017
概括
质母细胞通过中性过程驱动瘤生长. 化疗会扩大抗药性细胞, 但表观遗传化合物为质母细胞瘤提供新的治疗策略.
科学领域:
- 神经瘤学
- 癌症干细胞生物学
- 瘤发生
背景情况:
- 质母细胞 (GBM) 是由质母细胞 (GSC) 的子群驱动的.
- 在GBM中功能异质性的起源尚不清楚.
- 了解GSC的行为对于开发有效的GBM疗法至关重要.
研究的目的:
- 调查克隆细胞的进化和命运行为.
- 阐明GBM内异质性的潜在机制.
- 确定质母细胞瘤的潜在治疗点.
主要方法:
- 人类质母细胞细胞的连续移植.
- 克隆进化和繁殖动态的分析.
- 对GSC群体的化疗效应的评估.
- 对GSC向的表观遗传化合物的评估.
主要成果:
- GBM 克隆的生长遵循一个中立的过程,并保持根植于 GSC 的繁殖等级.
- 一个类似干细胞的细胞群产生快速循环的原生细胞和非增殖细胞.
- 化疗促进了先前存在的抗药性GSC的扩张.
- 罕见的"异常"克隆表现出不同的动态.
- 功能上不同的GSC可以被表观遗传化合物准.
结论:
- GBM 异质性源于由 GSC 控制的中性进化过程.
- 目前的化疗可能会无意中选择耐药的GSC.
- 针对不同的GSC的表观遗传疗法代表了质母细胞瘤的有希望的治疗途径.
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