Here, we demonstrate induction and long-term maintenance of TotiSCs from mouse pluripotent stem cells (PSCs) by a combination of three small molecules, TTNPB, 1-Azakenpaullone, and WS6
These cells, which we designated as ciTotiSCs (chemically induced totipotent stem cells), resembled mouse totipotent 2C-embryo stage cells at transcriptome, epigenome and metabolome level
In addition, ciTotiSCs exhibited bidirectional developmental potentials and were able to produce both embryonic and extraembryonic cells in vitro and in teratoma
Our chemical approach for TotiSCs induction and maintenance provides a defined in vitro system to manipulate and understand totipotent state towards creating life from non-germline