Stochastic promoter activation affects Nanog expression variability in mouse embryonic stem cells

Area of Science:

• Stem cell biology
• Molecular genetics
• Developmental biology

Background:

• Mouse embryonic stem cells (mESCs) exhibit self-renewal and pluripotency.
• Cell-to-cell heterogeneity in gene expression, particularly for Nanog, is observed in mESCs.
• Mechanisms underlying Nanog expression variability are not fully understood.

Purpose of the Study:

• To quantitatively analyze Nanog transcription in mESCs.
• To determine the contribution of intrinsic noise to Nanog expression variability.
• To investigate the relationship between Nanog mRNA and protein levels.

Main Methods:

• Quantitative analysis of Nanog transcription.
• Allele-specific single-molecule RNA fluorescent in situ hybridization in a reporter cell line.
• Correlation analysis of Nanog mRNA and protein levels.

Main Results:

• Nanog transcription is infrequent, pulsatile, and stochastic.
• Intrinsic noise accounts for approximately 45% of Nanog expression variability.
• Nanog mRNA and protein levels are well correlated within individual cells.

Conclusions:

• Stochastic promoter activation significantly influences Nanog expression variability in mESCs.
• Intrinsic noise plays a crucial role in generating cell-to-cell heterogeneity for pluripotency factors.
• Understanding Nanog heterogeneity is key to deciphering cell fate decisions in stem cells.