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Current single-cell RNA-seq approaches are hindered by preamplification bias, loss of strand of origin information, and the inability to observe small-RNA and mRNA dual transcriptomes. Here, we introduce a single-cell holo-transcriptome sequencing (Holo-Seq) that overcomes all three hurdles. Holo-Seq has the same quantitative accuracy and uniform coverage with a complete strand of origin information as bulk RNA-seq. Most importantly, Holo-Seq can simultaneously observe small RNAs and mRNAs in a single cell. Furthermore, we acquire small RNA and mRNA dual transcriptomes of 32 human hepatocellular carcinoma single cells, which display the genome-wide super-enhancer activity and hepatic neoplasm kinetics of these cells.
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Xiao et al. (2018) studied this question.
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