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Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
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Sequences are fundamental mathematical objects consisting of ordered lists of numbers that follow a specific rule or pattern. Sequences are critical in various mathematical concepts, including calculus, series, and number theory. They can model real-world phenomena such as population growth, financial investments, and physical processes like the diminishing height of a bouncing ball.Each number in a sequence is referred to as a term. Typically, the terms are denoted as a1, a2, a3,…, where...
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An arithmetic sequence is a structured arrangement of numbers where each term is derived by adding a constant value, known as the common difference, to the previous term. This consistent pattern allows for the efficient computation of any term within the sequence as well as the cumulative sum of multiple terms. The formula for finding the nth term of an arithmetic sequence is:Here, aₙ represents the nth term of the sequence, a is the first term, d is the common difference, and n is the...
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Updated: Feb 3, 2026

RNA-seq Analysis of Transcriptomes in Thrombin-treated and Control Human Pulmonary Microvascular Endothelial Cells
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Holo-Seq: single-cell sequencing of holo-transcriptome.

Zhengyun Xiao1, Guo Cheng1, Yang Jiao1

  • 1Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, 310058, Zhejiang, People's Republic of China.

Genome Biology
|October 19, 2018
PubMed
Summary
This summary is machine-generated.

Single-cell holo-transcriptome sequencing (Holo-Seq) overcomes limitations of current methods, enabling accurate, strand-specific mRNA and small RNA analysis. This new technique provides comprehensive insights into cellular gene expression and disease kinetics.

Keywords:
Anti-sense transcriptLiver cancerSingle cellSmall-RNA-SeqSuper-enhancerTotal RNA-SeqmRNA-Seq

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Area of Science:

  • Molecular Biology
  • Genomics
  • Bioinformatics

Background:

  • Current single-cell RNA sequencing (scRNA-seq) methods face challenges including preamplification bias, loss of strand information, and inability to analyze both small RNA and messenger RNA (mRNA) simultaneously.
  • These limitations hinder comprehensive understanding of cellular gene expression and regulation at the single-cell level.

Purpose of the Study:

  • To introduce a novel single-cell sequencing method, Holo-Seq, designed to overcome the limitations of existing scRNA-seq techniques.
  • To enable simultaneous, accurate, and strand-specific analysis of both small RNAs and mRNAs within individual cells.

Main Methods:

  • Development and implementation of Holo-Seq, a single-cell holo-transcriptome sequencing technology.
  • Application of Holo-Seq to analyze 32 single cells from human hepatocellular carcinoma (liver cancer).

Main Results:

  • Holo-Seq demonstrates quantitative accuracy and uniform coverage comparable to bulk RNA sequencing, with complete strand of origin information.
  • The method successfully captures both small RNA and mRNA transcriptomes simultaneously from single cells.
  • Analysis of hepatocellular carcinoma cells revealed genome-wide super-enhancer activity and hepatic neoplasm kinetics.

Conclusions:

  • Holo-Seq provides a robust solution for single-cell transcriptomics, addressing key limitations of previous methods.
  • The ability to perform dual small RNA and mRNA transcriptome analysis in single cells opens new avenues for studying gene regulation and disease mechanisms.
  • Holo-Seq offers valuable insights into the molecular landscape of complex diseases like hepatocellular carcinoma.