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
Zeb2 Regulates Cell Fate at the Exit from Epiblast State in Mouse Embryonic Stem Cells
Agata Stryjewska,Ruben Dries,Tim Pieters,Griet Verstappen,Andrea Conidi,Kathleen Coddens,Annick Francis,Lieve Umans,Wilfred F. J. van IJcken,Geert Berx,Leo A. van Grunsven,Frank Grosveld,Steven Goossens,Jody J. Haigh,Danny Huylebroeck +14 more
TL;DR: Zeb2 is critical in ESCs for exit from the epiblast state, and links the pluripotency network and DNA‐methylation with irreversible commitment to differentiation.
Journal ArticleDOI
The Art of Capturing Pluripotency: Creating the Right Culture
Qi-Long Ying,Austin Smith +1 more
TL;DR: It is found that mouse ESCs can be derived and maintained with high efficiency through insulation from differentiation cues combined with consolidation of an innate cell proliferation program and the outstanding challenge of generating naive pluripotent stem cells from different mammals.
Journal ArticleDOI
FGF signalling as a mediator of lineage transitions—Evidence from embryonic stem cell differentiation
TL;DR: The role of FGF signalling in early development is reviewed alongside the ES cell data and it is suggested that FGF dependent signalling via phospho‐Erk activation maybe a major mediator of transitions in lineage specification.
Journal ArticleDOI
Derivation of Hypermethylated Pluripotent Embryonic Stem Cells With High Potency
Siqin Bao,Walfred W. C. Tang,Baojiang Wu,Shinseog Kim,Shinseog Kim,Jingyun Li,Lin Li,Toshihiro Kobayashi,Caroline Lee,Yanglin Chen,Mengyi Wei,Shudong Li,Sabine Dietmann,Fuchou Tang,Xihe Li,M. Azim Surani +15 more
TL;DR: Properties of ASCs suggest that they represent cells at an intermediate cellular state between the naive and primed states of pluripotency, which is developmentally beyond the pluripotent cells in the inner cell mass but with higher potency than EpiSCs.
Journal ArticleDOI
Human and Mouse Induced Pluripotent Stem Cells Are Differentially Reprogrammed in Response to Kinase Inhibitors
Kunio Hirano,Shogo Nagata,Shinpei Yamaguchi,Masato Nakagawa,Keisuke Okita,Hidetoshi Kotera,Justin F. X. Ainscough,Takashi Tada +7 more
TL;DR: It is demonstrated that flat-shaped hiPSC colonies can be reprogrammed into bowl-shaped multi-potent stem cells (2i-hiPSCs) by using 2i+LIF medium, and gene expression profiling demonstrated that 2i-HIPSCs more closely resemble primitive neural stem Cells (PNSCs).
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.