Chemical reversion of mouse post-implantation epiblast directly to totipotent-like cells

Mouse totipotent-like cells (TLCs) have been generated from undifferentiated pluripotent embryonic stem cells (ESCs). However, it remains unknown whether TLCs can be generated from differentiated cells.

Here, we report a novel chemically defined medium which can efficiently induce TLCs from differentiation-committed cells including epiblast-like cells (EpiLCs) and post-implantation epiblast. Comparatively, MERVL-GFP positive cells induced from differentiated cells exhibit closer transcriptome characteristics to 2-cell (2C) embryos in contrast to those induced from pluripotent ESCs. Moreover, differentiated cells exhibit distinct reprogramming kinetics and pathways to TLCs compared to ESCs.