Joint single-cell multiomic analysis in Wnt3a induced asymmetric stem cell division

Area of Science:

• Stem cell biology
• Epigenetics
• Single-cell genomics

Background:

• Wnt signaling gradients regulate stem cell fate.
• Asymmetric cell division is crucial for development.
• Understanding epigenome-transcriptome dynamics is key to stem cell fate decisions.

Purpose of the Study:

• To develop a method for joint epigenome and transcriptome profiling in single cells.
• To investigate the role of H3K27me3 and H3K4me3 in Wnt3a-induced asymmetric cell division.
• To map cell type-specific epigenome and transcriptome changes in daughter cells.

Main Methods:

• Developed and utilized same cell epigenome and transcriptome sequencing (scEpiT-seq).
• Profiled H3K27me3, H3K4me3, and gene expression in mouse embryonic stem cells.
• Analyzed epigenomic and transcriptomic data from single, divided daughter cells.

Main Results:

• Identified cell type-specific epigenome and transcriptome maps in daughter cells.
• Demonstrated that H3K27me3, not H3K4me3, correlates with gene expression changes during asymmetric division.
• Showed that H3K27me3-defined cell clusters align with gene expression-defined clusters.

Conclusions:

• scEpiT-seq is a powerful tool for joint epigenome-transcriptome analysis in single cells.
• H3K27me3 plays a significant role in regulating gene expression during stem cell fate determination.
• Mechanistic insights into maintaining and resetting stem cell fate during differentiation were revealed.