Acquisition of 2C-like totipotency through defined maternal-effect factors.

Fully grown oocytes have the natural ability to transform two terminally differentiated gametes into a totipotent zygote representing acquisition of totipotency. This process wholly depends on maternal-effect factors (MFs). MFs stored in the eggs are therefore likely to be able to induce cellular reprogramming to a totipotency state. Here we report the generation of totipotent-like stem cells from mESCs using 4MFs Hsf1, Zar1, Padi6 and Npm2, designated as MFiTLSCs. MFiTLSCs exhibited unique and inherent capability to differentiate into embryonic and extraembryonic derivatives. Transcriptomic analysis revealed that MFiTLSCs are enriched with 2-cell-specific genes that appear to synergistically induce a transcriptional repressive state, in that parental genomes are remodelled to a poised transcriptional repression state while totipotency is established following fertilization. This method to derive MFiTLSCs could help advance understanding of fate determinations of totipotent stem cells in a physiological context and establish a foundation for development of oocyte biology-based reprogramming technology.