Global transcriptional analysis of mouse totipotent potential stem cells and extended pluripotent stem cells

It is challenging to derive totipotent stem cells in vitro that functionally and molecularly resemble cells from totipotent embryos. Here, we report that a chemical cocktail enables the derivation of totipotent-like stem cells, designated as totipotent potential stem (TPS) cells, from 2-cell mouse embryos and extended pluripotent stem cells that can be stably maintained long-term in vitro. TPS cells shared transcriptomic features with 2-cell mouse embryos and express totipotent markers. In vivo chimeric assays show that these cells have embryonic and extraembryonic developmental potentials at the single cell level. Moreover, we show that TPS cells can be induced into blastocyst-like structures resembling preimplantation mouse blastocysts. Our study demonstrates the feasibility of capturing and maintaining totipotency in vitro. Overall design: Total of 12 samples were analyzed, which include mouse totipotent potential stem cells and extended pluripotent stem cells. For mouse totipotent potential stem cells, 3 cell lines were analyzed, which include 2 technicial replicates for each cell line. For mouse extended pluripotent stem cells, 3 cell lines were analyzed, which include 2 technicial replicates for each cell line.