Differentiation is accompanied by a progressive loss in transcriptional memory

Area of Science:

• Molecular Biology
• Cell Biology
• Genomics

Background:

• Cell differentiation balances transcriptional memory with gene expression variability.
• Phenotypic change during differentiation depends on increased gene expression variability.
• The rate of transcriptome divergence in early cell divisions during differentiation is unknown.

Purpose of the Study:

• To investigate the rate of transcriptome divergence in early cell divisions during differentiation.
• To quantify changes in gene expression variability during the initial stages of cell differentiation.

Main Methods:

• Developed experimental methods to recover transcriptomes of related cells post-division, preserving lineage information.
• Analyzed transcriptomes of related cells from human CD34+ cells and chicken T2EC progenitors.
• Utilized single-cell RT-qPCR (scRT-qPCR) and single-cell RNA sequencing (scRNA-seq) technologies.

Main Results:

• Differentiating sister cells exhibit more similar gene transcription profiles than non-related cells.
• Greater transcriptional discrepancies were observed between differentiating sister cells compared to self-renewing sister cells.
• Transcriptome divergence progressively increased from the first to the second cell generation in differentiating cells.

Conclusions:

• Cell differentiation involves a gradual erasure of transcriptional memory.
• Gene expression variability increases significantly during early cell divisions in differentiating cells.
• Sister cells undergoing differentiation diverge more rapidly than those in self-renewal.