1, 2 The totipotent potential of early-stage blastomeres is gradually restricted at the blastocyst stage, when differentiation into epiblast, trophectoderm and primitive endoderm occurs. Our study opens up a new path toward fully capturing totipotent stem cells in vitro.ĭuring development, early-stage blastomeres are totipotent cells that have the potential to generate an entire individual, including both embryonic and extraembryonic components, at the single-cell level. Mechanistically, inhibition of HDAC1/2 and DOT1L activity and activation of RARγ signaling are important for inducing and maintaining totipotent features of TPS cells. Moreover, TPS cells can be induced into blastocyst-like structures resembling preimplantation mouse blastocysts. In vivo chimera formation assays show that these cells have embryonic and extraembryonic developmental potentials at the single-cell level. TPS cells shared features with 2-cell mouse embryos in terms of totipotency markers, transcriptome, chromatin accessibility and DNA methylation patterns. 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, and that these TPS cells can be stably maintained long term in vitro.
It is challenging to derive totipotent stem cells in vitro that functionally and molecularly resemble cells from totipotent embryos.
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