期刊
NATURE
卷 550, 期 7676, 页码 393-397出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature24052
关键词
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资金
- Wellcome Trust
- Portuguese Foundation for Science and Technology, FCT [SFRH/BD/84964/2012]
- Japan Society for the Promotion of Science
- National Institutes of Health [RP-PG-0310-10002]
- European Molecular Biology Organization [ALTF938-2014]
- Marie Sklodowska-Curie Individual Fellowship
- Biotechnology and Biological Sciences Research Council [BB/K010867/1]
- Wellcome Trust [095645/Z/11/Z, SCI 097922/Z/11/Z, 098051, 206194]
- Bloodwise [12029]
- Cancer Research UK [C1163/A12765, C1163/A21762]
- Leading Advanced Projects for Medical Innovation, Japan Agency for Medical Research and Development
- National Health and Medical Research Council [1110751]
- National Natural Science Foundation of China [81671579, 31370904, 30972691]
- National Key Research and Development Program [2017YFA0104500]
- BBSRC [BBS/E/B/000C0403, BB/K010867/1, BBS/E/B/0000H334] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BBS/E/B/0000H334, BBS/E/B/000C0403] Funding Source: researchfish
- Cancer Research UK [22310] Funding Source: researchfish
- Medical Research Council [MC_PC_12009] Funding Source: researchfish
- Fundação para a Ciência e a Tecnologia [SFRH/BD/84964/2012] Funding Source: FCT
Mouse embryonic stem cells derived from the epiblast(1) 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 endoderm(2) 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.
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