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
Transcription Factors for the Modulation of Pluripotency and Reprogramming
TL;DR: Comparing human and mouse ESCs will shed new light on the design of transcriptional regulatory networks for pluripotency, and the different roles of transcription factors in the modulation of pluripotent states and in the induction of plurIPotent phenotypes are summarized.
Journal ArticleDOI
Stem cells bioprocessing: an important milestone to move regenerative medicine research into the clinical arena.
Julia M. Polak,Sakis Mantalaris +1 more
TL;DR: This concise review deals with current achievements in the field, challenges that lie ahead and potential ways of having robust and reliable “off the shelf” cellular products.
Journal ArticleDOI
Genomic Approaches to Deconstruct Pluripotency
Yuin-Han Loh,Lin Yang,Jimmy C. Yang,Hu Li,James J. Collins,James J. Collins,James J. Collins,George Q. Daley,George Q. Daley +8 more
TL;DR: Recent advances gleaned from application of global "omics" techniques to dissect the molecular mechanisms that define the pluripotent state of ESCs and iPSCs are discussed.
Journal ArticleDOI
Human embryonic stem cells contribute to embryonic and extraembryonic lineages in mouse embryos upon inhibition of apoptosis.
Xuepeng Wang,Tianda Li,Tongtong Cui,Dawei Yu,Chao Liu,Liyuan Jiang,Liyuan Jiang,Guihai Feng,Lei Wang,Rui Fu,Xin-Xin Zhang,Xin-Xin Zhang,Jie Hao,Yukai Wang,Liu Wang,Qi Zhou,Wei Li,Baoyang Hu +17 more
TL;DR: Human embryonic stem cells contribute to embryonic and extraembryonic lineages in mouse embryos upon inhibition of apoptosis.
Journal ArticleDOI
A Sprouty4 reporter to monitor FGF/ERK signaling activity in ESCs and mice
Sophie M. Morgani,Néstor Saiz,Vidur Garg,Dhruv Raina,Claire S. Simon,Minjung Kang,Alfonso Martinez Arias,Jennifer Nichols,Christian Schröter,Anna-Katerina Hadjantonakis,Anna-Katerina Hadjantonakis +10 more
TL;DR: Genetic and chemical disruption of FGF/ERK signaling, in vivo in pre- and post-implantation embryos, abrogated Venus expression establishing the reporter as an accurate signaling readout, and this tool will provide new insights into the dynamics of the FGF / ERK signaling pathway during mammalian development.
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.