Establishment of mouse expanded potential stem cells

Cultures of expanded potential stem cells can be established from individual eight-cell blastomeres, and by direct conversion of mouse embryonic stem cells and induced pluripotent stem cells, highlighting the feasibility of establishing expanded potential stem cells for other mammalian species. Embryonic stem cells derived from mouse blastocyst can participate in somatic and germline lineages when reintroduced into mouse embryos, but they cannot produce extra-embryonic tissues. Pentao Liu and colleagues derived stem cells with expanded potential that can participate in both embryonic and extra-embryonic lineages from individual eight-cell blastomeres, or by direct conversion from pluripotent stem cells. These stem cells can also be used to obtain trophoblast stem cells, which differentiate into placenta cells, and extra-embryonic endoderm lines, which generate a nutritive support system for the embryo. Such expanded potential has been difficult to achieve so far. The derivation conditions identified by the authors could enable cells with similar properties to be obtained from other mammalian species. Mouse embryonic stem cells derived from the epiblast1 contribute to the somatic lineages and the germline but are excluded from the extra-embryonic tissues that are derived from the trophectoderm and the primitive endoderm2 upon reintroduction to the blastocyst. Here we report that cultures of expanded potential stem cells can be established from individual eight-cell blastomeres, and by direct conversion of mouse embryonic stem cells and induced pluripotent stem cells. Remarkably, a single expanded potential stem cell can contribute both to the embryo proper and to the trophectoderm lineages in a chimaera assay. Bona fide trophoblast stem cell lines and extra-embryonic endoderm stem cells can be directly derived from expanded potential stem cells in vitro. Molecular analyses of the epigenome and single-cell transcriptome reveal enrichment for blastomere-specific signature and a dynamic DNA methylome in expanded potential stem cells. The generation of mouse expanded potential stem cells highlights the feasibility of establishing expanded potential stem cells for other mammalian species.