Journal ArticleDOI
Derivation of pluripotent epiblast stem cells from mammalian embryos
I. Gabrielle M. Brons,Lucy E. Smithers,Matthew Trotter,Peter J. Rugg-Gunn,Bowen Sun,Susana M. Chuva de Sousa Lopes,Sarah K. Howlett,Amanda Clarkson,Lars Ährlund-Richter,Roger A. Pedersen,Ludovic Vallier +10 more
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TLDR
It is shown that pluripotent stem cells can be derived from the late epiblast layer of post-implantation mouse and rat embryos using chemically defined, activin-containing culture medium that is sufficient for long-term maintenance of human embryonic stem cells.Abstract:
Although the first mouse embryonic stem (ES) cell lines were derived 25 years ago using feeder-layer-based blastocyst cultures, subsequent efforts to extend the approach to other mammals, including both laboratory and domestic species, have been relatively unsuccessful. The most notable exceptions were the derivation of non-human primate ES cell lines followed shortly thereafter by their derivation of human ES cells. Despite the apparent common origin and the similar pluripotency of mouse and human embryonic stem cells, recent studies have revealed that they use different signalling pathways to maintain their pluripotent status. Mouse ES cells depend on leukaemia inhibitory factor and bone morphogenetic protein, whereas their human counterparts rely on activin (INHBA)/nodal (NODAL) and fibroblast growth factor (FGF). Here we show that pluripotent stem cells can be derived from the late epiblast layer of post-implantation mouse and rat embryos using chemically defined, activin-containing culture medium that is sufficient for long-term maintenance of human embryonic stem cells. Our results demonstrate that activin/Nodal signalling has an evolutionarily conserved role in the derivation and the maintenance of pluripotency in these novel stem cells. Epiblast stem cells provide a valuable experimental system for determining whether distinctions between mouse and human embryonic stem cells reflect species differences or diverse temporal origins.read more
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Journal ArticleDOI
Mettl14 is required for mouse postimplantation development by facilitating epiblast maturation.
Tie Gang Meng,Xukun Lu,Lei Guo,Guan Mei Hou,Xue Shan Ma,Qian Nan Li,Lin Huang,Li Hua Fan,Zheng Hui Zhao,Xiang Hong Ou,Ying Chun Ouyang,Heide Schatten,Lei Li,Zhen-Bo Wang,Qing-Yuan Sun +14 more
TL;DR: Mettl14 is indispensable for postimplantation embryonic development by facilitating the conversion from naive to primed state of the epiblast, and the critical function of METTL14 as an m6A modification regulator in orchestrating early mouse embryogenesis is highlighted.
Journal ArticleDOI
The role of pluripotency gene regulatory network components in mediating transitions between pluripotent cell states.
TL;DR: Re-expressing specific transcription factors operating within a pluripotency gene regulatory network (PGRN) can move cells back to an earlier developmental identity and is being applied to attempt establishment of human cell lines with the properties of mouse ES cells.
Journal ArticleDOI
The pluripotency factor Nanog regulates pericentromeric heterochromatin organization in mouse embryonic stem cells
Clara Lopes Novo,Calvin Tang,Kashif Ahmed,Ugljesa Djuric,Eden Fussner,Nicholas P. Mullin,Natasha P. Morgan,Jasvinder Hayre,Arnold R. Sienerth,Sarah Elderkin,Ryuichi Nishinakamura,Ian Chambers,James Ellis,David P. Bazett-Jones,Peter J. Rugg-Gunn +14 more
TL;DR: These results establish a direct connection between the pluripotency network and chromatin organization and emphasize that maintaining an open heterochromatin architecture is a highly regulated process in embryonic stem cells.
Journal ArticleDOI
Gene expression profiles of human inner cell mass cells and embryonic stem cells.
Renee A. Reijo Pera,Christopher DeJonge,Nancy L. Bossert,Mylene W.M. Yao,Jean Yee Hwa Yang,Narges Bani Asadi,Wing Hung Wong,Wong Connie C,Meri T. Firpo +8 more
TL;DR: Comparison of global gene expression between individual ICM clusters and human embryonic stem cells indicated that these two cell types are significantly different in regards to gene expression, with fewer than one half of all genes expressed in both cell types.
Journal ArticleDOI
X-chromosome inactivation in rett syndrome human induced pluripotent stem cells.
TL;DR: The inconsistencies in XCI status of RTT-hiPSCs generated to date are interpreted by comparison to other pluripotent systems in vitro and in vivo and the methods used to analyze XCI are discussed.
References
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Journal ArticleDOI
Embryonic Stem Cell Lines Derived from Human Blastocysts
James A. Thomson,Joseph Itskovitz-Eldor,Sander S. Shapiro,Michelle A. Waknitz,Swiergiel Jennifer J,Vivienne S. Marshall,Jeffrey M. Jones +6 more
TL;DR: Human blastocyst-derived, pluripotent cell lines are described that have normal karyotypes, express high levels of telomerase activity, and express cell surface markers that characterize primate embryonic stem cells but do not characterize other early lineages.
Journal ArticleDOI
Establishment in culture of pluripotential cells from mouse embryos
TL;DR: The establishment in tissue culture of pluripotent cell lines which have been isolated directly from in vitro cultures of mouse blastocysts are reported, able to differentiate either in vitro or after innoculation into a mouse as a tumour in vivo.
Journal ArticleDOI
Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells
TL;DR: In this article, the authors described the establishment directly from normal preimplantation mouse embryos of a cell line that forms teratocarcinomas when injected into mice and demonstrated the pluripotency of these embryonic stem cells by the observation that subclonal cultures, derived from isolated single cells, can differentiate into a wide variety of cell types.
Journal ArticleDOI
Core transcriptional regulatory circuitry in human embryonic stem cells.
Laurie A. Boyer,Tong Ihn Lee,Megan F. Cole,Sarah E. Johnstone,Stuart S. Levine,Jacob P. Zucker,Matthew G. Guenther,Roshan M. Kumar,Heather L. Murray,Richard G. Jenner,David K. Gifford,David K. Gifford,David K. Gifford,Douglas A. Melton,Douglas A. Melton,Rudolf Jaenisch,Richard A. Young,Richard A. Young +17 more
TL;DR: Insight is provided into the transcriptional regulation of stem cells and how OCT4, SOX2, and NANOG contribute to pluripotency and self-renewal and how they collaborate to form regulatory circuitry consisting of autoregulatory and feedforward loops.
Journal ArticleDOI
Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells.
TL;DR: A role is established for Oct-3/4 as a master regulator of pluripotency that controls lineage commitment and the sophistication of critical transcriptional regulators is illustrated and the consequent importance of quantitative analyses are illustrated.