Biased Allelic Expression in Human Primary Fibroblast Single Cells
Biased Allelic Expression in Human Primary Fibroblast Single Cells
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DOI：
10.1016/j.ajhg.2014.12.001
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发表时间：
2015-01-08
影响因子：
9.8
通讯作者：
Antonarakis, Stylianos E.
中科院分区：
文献类型：
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作者：
Borel, Christelle;Ferreira, Pedro G.;Antonarakis, Stylianos E.
通过基因组技术对哺乳动物单细胞中基因表达的研究为研究等位基因的表达模式提供了可能。我们使用单细胞RNA测序来检测203个单个人原代成纤维细胞中超过133，633个独特杂合单核苷酸变体（hetSNV）的等位基因特异性mRNA水平。我们观察到，在分析的快照中，每个细胞主要包含来自大多数基因的一个等位基因的转录物;事实上，76.4%的hetSNV在单细胞中显示随机的单等位基因表达。值得注意的是，相邻的hetSNV表现出单倍型一致的等位基因比例;相反，位于两个不同基因的远端位点独立于单倍型结构。此外，在单个细胞中的等位基因特异性表达与细胞转录本的丰度相关。我们观察到，在给定的时间点，在大多数单细胞中表达两个等位基因的基因是罕见的，并且富含高表达基因。鉴于我们根据基因观察到相关的单细胞等位基因谱，细胞中每个等位基因的相对丰度受到一些调控机制的控制。总的来说，这些结果对细胞表型变异性有直接影响。
The study of gene expression in mammalian single cells via genomic technologies now provides the possibility to investigate the patterns of allelic gene expression. We used single-cell RNA sequencing to detect the allele-specific mRNA level in 203 single human primary fibroblasts over 133,633 unique heterozygous single-nucleotide variants (hetSNVs). We observed that at the snapshot of analyses, each cell contained mostly transcripts from one allele from the majority of genes; indeed, 76.4% of the hetSNVs displayed stochastic monoallelic expression in single cells. Remarkably, adjacent hetSNVs exhibited a haplotype-consistent allelic ratio; in contrast, distant sites located in two different genes were independent of the haplotype structure. Moreover, the allele-specific expression in single cells correlated with the abundance of the cellular transcript. We observed that genes expressing both alleles in the majority of the single cells at a given time point were rare and enriched with highly expressed genes. The relative abundance of each allele in a cell was controlled by some regulatory mechanisms given that we observed related single-cell allelic profiles according to genes. Overall, these results have direct implications in cellular phenotypic variability.