Diverse development potency and metabolic shape of extended pluripotency are faithfully transferred to somatic cells via cell fusion reprogramming

Extended pluripotent stem cells (EPSCs) are a novel cell type derived from 8-cell stage embryo or conversion of pluripotent stem cells using a chemical cocktail that blocks the cell fate decision. Previous studies have defined various aspects of EPSCs including dual differentiational potency to both extraembryonic and embryonic lineages, their ability to directly transfer extended pluripotency to differentiated somatic cells by cell fusion remains unelucidated. Here, we sought to determine whether somatic cells could be reprogrammed and obtain extended pluripotency. In this study, newly derived EPSCs are fused with neural stem cells, which is somatic stem cells, by polyethylene glycol (PEG)-mediated method. The resulting hybrid cells exhibited pluripotential properties with upregulated EPSC-specific genes. Also, hybrid cells contributed to the embryonic and extraembryonic lineages in vivo and in vitro. RNA-sequencing analysis confirmed that the global gene expression pattern of hybrid cells are similar to EPSC while there is no expression of NSC markers, indicating complete erasure of somatic memory after fusion reprogramming. Lastly, EPSCs and hybrids exhibited a bivalent energy metabolism phenotype or more active oxidative phosphorylation (OXPHOS) and glycolysis than NSCs. In conclusion, the extended pluripotency of EPSCs could be transferred to somatic cells through fusion-induced reprogramming. Overall design: Global gene expression pattern reprogramming to the state of EPSCs after cell fusion has been verified by RNA-seq in EPSC, ESC, NSC, and hybrid cell.