TBX3 orchestrates H3K4 trimethylation for porcine induced pluripotent stem cells to totipotent-like stem cells1

Pluripotent stem cells (PSCs) are useful for developmental and translational research because they have the potential to differentiate into all cell types of an adult individual. Pigs are one of the most important domestic ungulates, commonly used for food and as bioreactors. Generating stable pluripotent porcine PSC lines remains challenging. So far, the pluripotency gene network of porcine PSCs is poorly understood. Here we found that TBX3-derived induced pluripotent stem cells (iPSCs) closely resemble porcine 4-cell embryos with the capacity of totipotent-like stem cells (TLSCs). Interestingly, our data suggest that TBX3 facilitates the activation of H3K4me3 methyltransferase, specifically MLL1. Subsequent investigations revealed that the porcine 4-cell specific gene, MCL1, is a key downstream effector of the TBX3-MLL1 axis. Together, our study of the TBX3 regulatory network is helpful in the understanding of the totipotency characteristics of pigs.