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癌细胞克隆转录和表观遗传状态维持的机制
2020-06-30 19:48

以色列魏茨曼科学研究所Amos Tanay课题组通过单细胞分析,揭示了癌细胞克隆如何维持其转录和表观遗传状态。2020年6月29日,《自然-遗传学》发表了这一成果。

研究人员通过单细胞转录和DNA甲基化分析与Luria-Delbrück实验设计相结合的方法,证明多种类型的癌细胞中存在克隆稳定的表观遗传记忆。结肠癌克隆细胞群的纵向转录和遗传分析表明上皮到间充质转录特征的缓慢漂移谱,这似乎与遗传变异无关。DNA甲基化图谱与这些特征相关,但也反映了独特的节律样甲基化丢失过程。在大多数情况下,甲基化变化可以通过整体反式作用因子的作用来解释。

但是,对于特定类型的启动子,特别是癌症-睾丸抗原,去阻抑与顺式甲基化的丧失有关,并可能由其驱动。这项研究表明,通过表观遗传记忆可以使癌细胞中的基因亚克隆结构多样化。

研究人员表示,克隆调控程序的传播利于癌症发展。人们对表观遗传机制如何与遗传诱导因子相互作用以重塑这一过程了解甚少。

附:英文原文

Title: Single-cell analysis of clonal maintenance of transcriptional and epigenetic states in cancer cells

Author: Zohar Meir, Zohar Mukamel, Elad Chomsky, Aviezer Lifshitz, Amos Tanay

Issue&Volume: 2020-06-29

Abstract: Propagation of clonal regulatory programs contributes to cancer development. It is poorly understood how epigenetic mechanisms interact with genetic drivers to shape this process. Here, we combine single-cell analysis of transcription and DNA methylation with a Luria–Delbrück experimental design to demonstrate the existence of clonally stable epigenetic memory in multiple types of cancer cells. Longitudinal transcriptional and genetic analysis of clonal colon cancer cell populations reveals a slowly drifting spectrum of epithelial-to-mesenchymal transcriptional identities that is seemingly independent of genetic variation. DNA methylation landscapes correlate with these identities but also reflect an independent clock-like methylation loss process. Methylation variation can be explained as an effect of global trans-acting factors in most cases. However, for a specific class of promoters—in particular, cancer–testis antigens—de-repression is correlated with and probably driven by loss of methylation in cis. This study indicates how genetic sub-clonal structure in cancer cells can be diversified by epigenetic memory.

DOI: 10.1038/s41588-020-0645-y

Source: https://www.nature.com/articles/s41588-020-0645-y

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:25.455
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex


本期文章:《自然—遗传学》:Online/在线发表

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