A regulatory circuitry locking pluripotent stemness to embryonic stem cell: Interaction between threonine catabolism and histone methylation.

Mouse embryonic stem cell (ESC) is a prototype of pluripotent stem cell that undergoes endless self-renewal in culture without losing the pluripotency, the ability to differentiate to all somatic lineages. The self-renewal of ESC relies on a gene expression program, epigenetic state, and cellular metabolism specific to ESC. In this review, we will present the evidence to exemplify how gene regulation, chromatin methylation, and threonine catabolism are specialized to boost ESC self-renewal. It is evident that a feedforward regulatory circuitry forms at the interfaces between the transcriptional, epigenetic and metabolic control to consolidate the pluripotency of ESC.