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Establishment of mouse expanded potential stem cells

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Tanaka, Y 
Wilkinson, A 


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.



Animals, Blastocyst, Blastomeres, Cell Lineage, Cells, Cultured, Chimera, Embryo, Mammalian, Endoderm, Epigenesis, Genetic, Epigenomics, Female, Male, Mice, Mouse Embryonic Stem Cells, Placenta, Pluripotent Stem Cells, Pregnancy, Single-Cell Analysis, Transcriptome, Trophoblasts

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Nature Publishing Group
Cancer Research UK (21762)
Medical Research Council (MC_PC_12009)
Wellcome Trust (097922/Z/11/Z)
Leukaemia & Lymphoma Research (12029)
D.R. is a recipient of the Wellcome Trust Clinical PhD Fellowship for Academic Clinicians. L.A. is a recipient of a Ph.D. fellowship from the Portuguese Foundation for Sciences and Technology, FCT(SFRH/BD/84964/2012). Y. T. was supported by a Japan Society for the Promotion of Science fellowship. A.C.W. was supported by the National Institute of Health Research (RP-PG-0310-10002). M. E-M is supported by an EMBO Fellowship (ALTF938-2014) and Marie Sklodowska-Curie Individual Fellowship. W. R. acknowledges funding from BBSRC (BB/K010867/1) and Wellcome Trust (095645/Z/11/Z). L. Lu is supported by the National Natural Science Foundation of China (31370904 and 30972691). P. L. lab is supported by the Wellcome Trust (grant numbers: 098051 and 206194).