Dormancy represents a vital biological mechanism facilitating the continuity of various life forms across generations and in response to challenging environmental conditions. In the early stages of mammalian development, embryos can enter a state of dormancy known as diapause. In diapause they can remain viable within the uterus for extended periods, lasting from weeks to months. This dormancy state can be mimicked in vitro by inhibiting the central cellular growth pathway, mTOR. However, the cellular mechanisms that maintain the original cell identity amidst the transcriptionally silent landscape of dormancy remain elusive. This thesis demonstrates the significance of safeguarding cis-regulatory elements from transcriptional silencing to preserve pluripotency during dormancy. Further, this thesis elucidates a TET-transcription factor (TF) axis, wherein TET-mediated DNA demethylation and the recruitment of methylation-sensitive TFs orchestrate chromatin modifications essential for transitioning into dormancy. Disruption of TET activity compromises both pluripotency and the viability of dormant embryos, whereas its augmentation enhances survival rates. These findings uncover a critical mechanism governing the preservation of cellular identity during dormancy, with implications for regenerative medicine and understanding disease processes.
