Untargeted histone profiling during naive conversion uncovers conserved modification markers between mouse and human.

Area of Science:

• Stem cell biology
• Epigenetics
• Mammalian developmental biology

Background:

• Human embryonic stem cells (hESCs) can be converted to a naive pluripotent state, similar to mouse ESCs (mESCs).
• A detailed epigenetic characterization of this human conversion process is missing.
• The similarity between human and mouse naive pluripotency states requires further investigation.

Purpose of the Study:

• To comprehensively profile the histone epigenome during hESC conversion to the naive state.
• To establish a time-resolved roadmap of epigenetic changes.
• To compare human and mouse epigenetic signatures of naive pluripotency.

Main Methods:

• Utilized an untargeted mass spectrometry approach.
• Analyzed histone epigenome changes in hESCs during primed-to-naive conversion.
• Performed time-resolved profiling of histone post-translational modifications (hPTMs).

Main Results:

• Identified 23 significantly altered hPTMs during the conversion process.
• Observed a prominent increase in H3K27Me3 in naive hESCs, consistent with mouse ESCs.
• Revealed conserved hPTM markers and a shared mammalian epigenetic signature for the naive pluripotent state.

Conclusions:

• Presented the first roadmap of the human histone epigenome during primed-to-naive hESC conversion.
• Demonstrated similarities between human and mouse naive pluripotent states.
• Suggested a conserved mammalian epigenetic basis for the ground state of pluripotency.