Fig. 1. Comparative incongruence of murine and human embryonic and developmental stages.
Top: Murine ESC (mESC; red) are derived from pre-implantation morula- or blastocyst-staged murine embryos, and capture a naïve epiblast-like pluripotent state. mESCs can differentiate into all three germ-layers via in vitro directed differentiation, in vivo teratomas, and in vivo morula/blastocyst chimera assays. The murine pluripotent state can also be obtained through epigenetic reprogramming of somatic cells with ectopic expression of Yamanaka factors. Murine extended potential stem cells (mEPSCs; green) possess both embryonic and extra-embryonic differentiation potency and can be derived via chemical reprogramming of cleavage-stage murine blastomere cells of mESCs. Stem cells resembling the molecular phenotype of 2-cell (2C) cleavage-staged blastomeres (purple) putatively possessing totipotent-like molecular characteristics can be isolated from mESC cell cultures122, or through the inductive expression of key totipotent factors (e.g., Dux and NELF-A). Bottom: Although conventional hESC (blue) are similarly derived from the pre-implantation stages of IVF-derived morula or blastocyst-staged human embryos, they are phenotypically similar in culture with post-implantation primed murine epiblast stem cells (mEpiSC; blue). A primed, mEpiSC-like state of pluripotency is also attained through the epigenetic reprogramming of human somatic cells by Yamanaka factors into hiPSC. Multiple methods for reverting conventional hPSC to naïve human pluripotent stem cells (N-hPSC; red) with mESC-like pluripotency have been reported employing various small molecule inhibitor cocktails or via transgene expression of key factors10. Self-renewing human totipotent stem cells (purple) with phenotypic equivalence to four to eight-cell or cleavage stage human blastomeres have not yet been described.