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RNA-seq

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

A Combinatorial Single-cell Approach to Characterize the Molecular and Immunophenotypic Heterogeneity of Human Stem and Progenitor Populations

Published on: October 25, 2018

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

Summary

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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A Combinatorial Single-cell Approach to Characterize the Molecular and Immunophenotypic Heterogeneity of Human Stem and Progenitor Populations

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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.