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Related Concept Videos

RNA-seq03:21

RNA-seq

RNA sequencing, or RNA-Seq, is a high-throughput sequencing technology used to study the transcriptome of a cell. Transcriptomics helps to interpret the functional elements of a genome and identify the molecular constituents of an organism. Additionally, it also helps in understanding the development of an organism and the occurrence of diseases. 
Before the discovery of RNA-seq, microarray-based methods and Sanger sequencing were used for transcriptome analysis. However, while microarray-based...

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Updated: Jun 14, 2026

A Combinatorial Single-cell Approach to Characterize the Molecular and Immunophenotypic Heterogeneity of Human Stem and Progenitor Populations
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Combinatorial profiling of multiple histone modifications and transcriptome in single cells using scMTR-seq.

Yang Wang1, Jingyu Li1, Andrew A Malcolm1

  • 1Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK.

Science Advances
|August 6, 2025
PubMed
Summary
This summary is machine-generated.

A new method, single-cell multitargets and mRNA sequencing (scMTR-seq), simultaneously profiles six histone modifications and transcriptomes in single cells. This technique reveals dynamic epigenetic changes during human endoderm differentiation and mouse embryonic development.

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Area of Science:

  • Epigenetics and Genomics
  • Cellular and Molecular Biology
  • Developmental Biology

Background:

  • Mapping chromatin states in complex samples is challenging due to the lack of methods for simultaneous profiling of multiple histone modifications and transcriptomes in single cells.
  • Understanding combinatorial histone modifications is crucial for deciphering gene regulatory elements and epigenetic programs.
  • Previous methods were insufficient for high-throughput, multi-omic analysis at the single-cell level.

Purpose of the Study:

  • To develop and validate a novel high-throughput method for simultaneous profiling of multiple histone modifications and transcriptomes in single cells.
  • To investigate dynamic chromatin state and transcriptome changes during human endoderm differentiation.
  • To generate lineage-resolved chromatin maps and gene regulatory networks in mouse blastocysts.

Main Methods:

  • Development of single-cell multitargets and mRNA sequencing (scMTR-seq).
  • Application of scMTR-seq to profile six histone modifications and transcriptome simultaneously in single cells.
  • Analysis of human endoderm differentiation and mouse blastocyst development using scMTR-seq data.

Main Results:

  • scMTR-seq successfully enabled simultaneous profiling of six histone modifications and transcriptome in single cells.
  • Dynamic and coordinated changes in chromatin states and transcriptomes during human endoderm differentiation were uncovered.
  • Lineage-resolved chromatin maps and gene regulatory networks in mouse blastocysts were produced, revealing epigenetic asymmetries and identifying Trps1 as a potential repressor.

Conclusions:

  • scMTR-seq is a powerful tool for investigating combinatorial chromatin landscapes in heterogeneous samples.
  • The method provides novel insights into epigenetic regulatory systems and gene regulation during development.
  • scMTR-seq facilitates a deeper understanding of dynamic epigenetic changes and lineage specification.