Novel kinetic and developmental transcriptomic pan-stress responses by embryonic stem cells

Area of Science:

• Developmental Biology
• Reproductive Biology
• Genomics

Background:

• Early miscarriages are frequent, with environmental factors playing a significant role.
• The molecular mechanisms linking environmental stressors to embryo loss are not well understood.
• Mouse embryonic stem cells (ESC) serve as a valuable model for studying early developmental responses.

Purpose of the Study:

• To identify shared molecular markers ('pan-stress' genes) in ESC responding to various environmental insults.
• To investigate the potential of these markers as predictors of miscarriage risk.
• To explore the mechanisms underlying concordant gene expression changes under stress.

Main Methods:

• Exposed mouse ESC to control conditions and diverse environmental stressors at miscarriage-risk levels.
• Performed transcriptomic analysis using RNA sequencing to assess gene expression changes.
• Identified genes with significant and directionally concordant expression changes across stress conditions.

Main Results:

• Discovered a substantial set of 'pan-stress' genes exhibiting concordant directional changes from the stemness state.
• Identified 94 genes significantly altered under four weaker stressors and normal differentiation.
• A subset of 21 genes showed shared significance across weaker and two stronger stress stimuli, all with nonrandom directional changes.

Conclusions:

• Characterized a robust pan-stress response in ESC, indicating conserved molecular pathways.
• Identified potential transcription and secreted factors involved in mediating stress responses.
• These pan-stress genes represent promising biomarkers for miscarriage prediction and mechanistic studies.