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Nature. 2017 Oct 19;550(7676):393-397. doi: 10.1038/nature24052. Epub 2017 Oct 11.

Establishment of mouse expanded potential stem cells.

Author information

1
Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK.
2
Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge CB2 0RE, UK.
3
Division of Stem Cell Therapy, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
4
European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, Cambridge CB10 1SD, UK.
5
Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
6
Epigenetics Programme, The Babraham Institute, Cambridge CB22 3AT, UK.
7
Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK.
8
Wellcome Trust-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0XY, UK.
9
Division of Cellular Therapy, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
10
Embryology Unit, Children's Medical Research Institute, University of Sydney, Westmead, New South Wales 2145, Australia.
11
School of Medical Sciences, Sydney Medical School, University of Sydney, Westmead, New South Wales 2145, Australia.
12
Institute for Stem Cell Biology and Regenerative Medicine, Department of Genetics, Stanford University School of Medicine, Stanford, California 94305-5461, USA.
13
Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.

Abstract

Mouse embryonic stem cells derived from the epiblast 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 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.

PMID:
29019987
PMCID:
PMC5890884
DOI:
10.1038/nature24052
[Indexed for MEDLINE]
Free PMC Article

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