Maternal factor NELFA drives a 2C-like state in mouse embryonic stem cells

Area of Science:

• Developmental Biology
• Stem Cell Biology
• Epigenetics

Background:

• Mouse embryonic stem cells (ESCs) can spontaneously enter a 2-cell (2C) like state, marked by specific gene expression.
• Understanding the factors regulating this transition is crucial for developmental biology.

Purpose of the Study:

• To identify novel factors that induce the 2C-like state in mouse ESCs.
• To elucidate the mechanisms governing the transition from ESCs to the 2C-like state.

Main Methods:

• Identification of NELFA as a key factor in ESCs.
• Analysis of NELFA-Top2a interaction in the 2C-like state.
• Investigating the role of glycolysis in the 2C-like fate.
• Chromatin state analysis.

Main Results:

• Heterogeneous NELFA expression correlates with 2C gene upregulation and enhanced developmental potential.
• NELFA interacts with Top2a, driving Dux expression, a key regulator of the 2C state.
• Suppression of glycolysis chemically induces the 2C-like state.
• NELFA promotes the decommissioning of ESC-specific enhancers.

Conclusions:

• NELFA is identified as an early driver of the 2C-like state in mouse ESCs.
• The study reveals the interplay between NELFA, Top2a, Dux, and glycolysis in regulating the ESC to 2C-like transition.
• Findings suggest epigenetic reprogramming involving enhancer decommissioning is critical for this fate conversion.