Simultaneous profiling of transcriptome and DNA methylome from a single cell.
Simultaneous profiling of transcriptome and DNA methylome from a single cell.
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同时分析单个细胞的转录组和 DNA 甲基化组。
DOI：
10.1186/s13059-016-0950-z
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发表时间：
2016-05-05
期刊：
影响因子：
12.3
通讯作者：
Fan G
中科院分区：
文献类型：
--
作者：
Hu Y;Huang K;An Q;Du G;Hu G;Xue J;Zhu X;Wang CY;Xue Z;Fan G
单细胞转录组和单细胞甲基化技术已经成为在全基因组范围内研究单细胞RNA和DNA甲基化谱的有力工具。一个主要的挑战是理解DNA甲基化和单细胞内基因表达的直接关系。由于细胞间的差异很大，并且缺乏对同一细胞的转录组和甲基组的直接测量，因此这种关联仍然不清楚。在这里，我们描述了一种新的方法（scMT-seq），可以同时分析来自同一细胞的DNA甲基组和转录组。在感觉神经元中，我们一致发现单细胞之间的转录组和甲基组异质性，但除了不含CpG岛的基因外，大多数表达差异不能用近端启动子甲基化来解释。相比之下，只有那些含有CpG岛启动子的基因的基因体甲基化与基因表达呈正相关。此外，利用杂交小鼠模型的单核苷酸多态性模式，我们还发现等位基因体甲基化与等位基因表达呈正相关。我们的方法可用于检测单细胞内的转录组、甲基组和单核苷酸多态性信息，以剖析表观遗传基因调控的机制。本文的在线版本（doi:10.1186/s13059-016-0950-z）包含补充材料，可供授权用户使用。
Single-cell transcriptome and single-cell methylome technologies have become powerful tools to study RNA and DNA methylation profiles of single cells at a genome-wide scale. A major challenge has been to understand the direct correlation of DNA methylation and gene expression within single-cells. Due to large cell-to-cell variability and the lack of direct measurements of transcriptome and methylome of the same cell, the association is still unclear. Here, we describe a novel method (scMT-seq) that simultaneously profiles both DNA methylome and transcriptome from the same cell. In sensory neurons, we consistently identify transcriptome and methylome heterogeneity among single cells but the majority of the expression variance is not explained by proximal promoter methylation, with the exception of genes that do not contain CpG islands. By contrast, gene body methylation is positively associated with gene expression for only those genes that contain a CpG island promoter. Furthermore, using single nucleotide polymorphism patterns from our hybrid mouse model, we also find positive correlation of allelic gene body methylation with allelic expression. Our method can be used to detect transcriptome, methylome, and single nucleotide polymorphism information within single cells to dissect the mechanisms of epigenetic gene regulation. The online version of this article (doi:10.1186/s13059-016-0950-z) contains supplementary material, which is available to authorized users.