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Locus-specific expression of transposable elements in single cells with CELLO-seq
Nature Biotechnology ( IF 33.1 ) Pub Date : 2021-11-15 , DOI: 10.1038/s41587-021-01093-1
Rebecca V Berrens 1, 2 , Andrian Yang 3 , Christopher E Laumer 3 , Aaron T L Lun 1, 4 , Florian Bieberich 1, 5 , Cheuk-Ting Law 1, 6 , Guocheng Lan 1, 7 , Maria Imaz 8, 9 , Joseph S Bowness 2 , Neil Brockdorff 2 , Daniel J Gaffney 8, 10 , John C Marioni 1, 3, 8
Affiliation  

Transposable elements (TEs) regulate diverse biological processes, from early development to cancer. Expression of young TEs is difficult to measure with next-generation, single-cell sequencing technologies because their highly repetitive nature means that short complementary DNA reads cannot be unambiguously mapped to a specific locus. Single CELl LOng-read RNA-sequencing (CELLO-seq) combines long-read single cell RNA-sequencing with computational analyses to measure TE expression at unique loci. We used CELLO-seq to assess the widespread expression of TEs in two-cell mouse blastomeres as well as in human induced pluripotent stem cells. Across both species, old and young TEs showed evidence of locus-specific expression with simulations demonstrating that only a small number of very young elements in the mouse could not be mapped back to the reference with high confidence. Exploring the relationship between the expression of individual elements and putative regulators revealed large heterogeneity, with TEs within a class showing different patterns of correlation and suggesting distinct regulatory mechanisms.



中文翻译:


使用 CELLO-seq 在单细胞中进行转座元件的位点特异性表达



转座元件 (TE) 调节从早期发育到癌症的多种生物过程。年轻 TE 的表达很难用下一代单细胞测序技术来测量,因为它们的高度重复性意味着短的互补 DNA 读数无法明确地映射到特定基因座。单细胞长读长RNA测序(CELLO-seq)将长读长单细胞RNA测序与计算分析相结合,以测量独特基因座的TE表达。我们使用 CELLO-seq 评估了 TE 在两细胞小鼠卵裂球以及人类诱导多能干细胞中的广泛表达。在这两个物种中,年老和年轻的 TE 都显示出基因座特异性表达的证据,模拟表明小鼠中只有少数非常年轻的元素无法以高置信度映射回参考。探索单个元件的表达和假定的调节因子之间的关系揭示了很大的异质性,一类内的 TE 显示出不同的相关模式,并暗示了不同的调节机制。

更新日期:2021-11-15
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