Stimulus-triggered fate conversion of somatic cells into pluripotency

Area of Science:

• Cell biology
• Developmental biology
• Epigenetics

Background:

• Cellular reprogramming typically involves nuclear transfer or introducing specific transcription factors.
• Mammalian somatic cells possess a stable epigenetic state, making reprogramming challenging.

Purpose of the Study:

• To report a novel cellular reprogramming phenomenon, stimulus-triggered acquisition of pluripotency (STAP).
• To investigate the mechanism and potential applications of STAP in mammalian somatic cells.

Main Methods:

• Applying strong external stimuli, specifically a transient low-pH stressor, to mammalian somatic cells (lymphocytes).
• Utilizing real-time imaging and gene rearrangement analysis to track cellular changes.
• Assessing DNA methylation patterns in pluripotency gene regulatory regions.
• Performing blastocyst injection experiments to evaluate developmental potential.

Main Results:

• STAP successfully reprogrammed mammalian somatic cells into pluripotent cells without nuclear transfer or transcription factors.
• Evidence indicated reprogramming, not selection, was the mechanism, confirmed by real-time imaging and gene analysis.
• STAP cells exhibited reduced DNA methylation in pluripotency gene regions.
• STAP cells demonstrated efficient contribution to chimaeric embryos and germline transmission in offspring.
• Robustly expandable pluripotent cell lines were derived from STAP cells.

Conclusions:

• Environmental cues can significantly alter epigenetic fate determination in mammalian cells.
• STAP represents a unique and efficient method for generating pluripotent cells from somatic cells.
• This discovery opens new avenues for regenerative medicine and understanding cell plasticity.