长期淋巴细胞白血病的表观遗传进化和血统史
Federico Gaiti1,2, Ronan Chaligne1,2, Hongcang Gu3
1New York Genome Center, New York, NY, USA.
Nature
|May 17, 2019
概括
这项研究揭示了表皮化或DNA甲基化变化在癌症进化过程中起着分子时钟的作用. 在慢性淋巴细胞白血病 (CLL) 中分析单细胞有助于重建癌症血统并追踪治疗反应.
科学领域:
- 癌症生物学
- 表观遗传学
- 基因组学
背景情况:
- 由遗传和表观遗传变化驱动的瘤内部异质性影响了癌症的演变.
- 慢性淋巴细胞白血病 (CLL) 是癌症演变的一个模型,表现出基因多样化和表观遗传变化,如表观突变.
- 之前的批量测序研究无法在单细胞水平上解决CLL的表皮化模式.
研究的目的:
- 测量来自健康捐赠者和CLL患者的B细胞单细胞分辨率的表皮化率.
- 使用表皮化数据重建癌症血统并了解CLL的演变.
- 调查治疗引起的CLL血统偏差.
主要方法:
- 对B细胞进行多复合单细胞减少表现二硫酸盐测序 (scRRBS).
- 单细胞二硫酸盐测序与单细胞转录组和基因定型的整合.
- 在ibrutinib治疗期间对连续样本进行分析,以检查血统偏差.
主要成果:
- 与健康的B细胞不同,CLL表现出持续增加的表皮化率,细胞间的变异性较低,因分化年龄而变化.
- 与正常B细胞相比,表皮化数据使得高分辨率的血统重建成为可能,揭示了CLL早期的分支和更长的分支.
- 在CLL中,基因子克隆被映射到从表皮化数据推断出的不同类型.
- 特定的细胞类被确定为优选地从淋巴结中驱逐出ibrutinib治疗后,其特征是不同的转录特征.
结论:
- 表皮转移作为一个分子时钟, 绘制CLL血统历史和进化.
- 基因,表观遗传和转录数据的单细胞整合提供了癌症演变的全面视图.
- 皮质分析可以揭示CLL中治疗诱导的血统动态.
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