Decoding and engineering 3D chromatin interactions governing pluripotent and totipotent cell states

Cell fate plasticity - the capacity of cells to transition between distinct identities - is particularly evident in pluripotent and totipotent cells, including embryonic cells and their in vitro stem cell counterparts. Accumulating evidence indicates that these cell states are accompanied by extensive remodeling of three-dimensional (3D) chromatin organization, including changes in compartments, topologically associating domains, and enhancer-promoter interactions. Engineering chromatin architecture to modulate pluripotency- or totipotency-associated genes has emerged as a promising strategy to reprogram cell identity and acquire pluripotent or totipotent features. Realizing this potential, however, requires a comprehensive understanding of both the universal principles of 3D chromatin regulation and the mechanisms specific to pluripotency or totipotency. Here, we review recent advances linking 3D chromatin structure to pluripotency and totipotency, and outline future directions for elucidating their regulatory logic. We also highlight key open questions that must be addressed to harness 3D genome engineering for controlling cell pluripotency or totipotency.