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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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
Citations
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Journal ArticleDOI
Epigenetic differences between naïve and primed pluripotent stem cells.
TL;DR: It has been 8 years since the concept of naïve and primed pluripotent stem cell states was first proposed and the epigenetic differences that underlie the distinct developmental potential of these cell types remain unclear, which is rather surprising.
Journal ArticleDOI
Inhibition of Apoptosis Overcomes Stage-Related Compatibility Barriers to Chimera Formation in Mouse Embryos.
Hideki Masaki,Megumi Kato-Itoh,Yusuke Takahashi,Ayumi Umino,Hideyuki Sato,Keiichi Ito,Ayaka Yanagida,Toshinobu Nishimura,Tomoyuki Yamaguchi,Masumi Hirabayashi,Takumi Era,Kyle M. Loh,Sean M. Wu,Irving L. Weissman,Hiromitsu Nakauchi,Hiromitsu Nakauchi +15 more
TL;DR: It is shown that transient promotion of cell survival through expression of the anti-apoptotic gene BCL2 enables EpiSCs and Sox17+ endoderm progenitors to integrate into blastocysts and contribute to chimeric embryos, providing a method to overcome cellular compatibility issues that typically restrict chimera formation.
Journal ArticleDOI
DNA methylation profiles define stem cell identity and reveal a tight embryonic-extraembryonic lineage boundary.
Claire E. Senner,Claire E. Senner,Felix Krueger,David Oxley,Simon Andrews,Myriam Hemberger,Myriam Hemberger +6 more
TL;DR: Detailed methylation profiles identify a cohort of developmentally regulated sequence elements that will be most valuable to uncover novel transcriptional regulators and pivotal “gatekeeper” genes in pluripotency and lineage differentiation.
Journal ArticleDOI
Drug screening for human genetic diseases using iPSC models.
TL;DR: The foundational technologies that have enabled iPSCs, the power and limitations of iPSC-based compound screens along with screening guidelines, and recent examples of screening efforts are reviewed.
Journal ArticleDOI
Stem-cell-based embryo models for fundamental research and translation.
TL;DR: The recent emergence of stem-cell-derived embryo models, a new field aiming to use stem cells to construct in vitro models to recapitulate snapshots of the development of the mammalian conceptus, opens up exciting opportunities to promote fundamental understanding of human development and advance reproductive and regenerative medicine.
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.