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
Status of genomic imprinting in epigenetically distinct pluripotent stem cells.
Bowen Sun,Mitsuteru Ito,Sasha Mendjan,Yoko Ito,I. Gabrielle M. Brons,Adele Murrell,Ludovic Vallier,Anne C. Ferguson-Smith,Roger A. Pedersen +8 more
TL;DR: It is found that mouse induced pluripotent stem cells (iPSCs) tend to lose imprinting similar to mouse ESCs, confirming the view that hESCs and EpiSCs are in vitro counterparts, sharing an epigenetic status distinct from ESCs and iPSCs.
Journal ArticleDOI
Signaling Roadmap Modulating Naive and Primed Pluripotency
TL;DR: Accurate identification of the functions of major pluripotency-related signaling pathways and their cross-talk networks should aid in the successful induction of stable naive pluripotent states in human cells.
Journal ArticleDOI
Establishment of epigenetic patterns in development
Martin Leeb,Anton Wutz +1 more
TL;DR: The role of epigenetic regulation in the early mouse embryo, which presents a relatively well-understood system, is discussed and insights into this epigenetic “memory” of the first lineage decisions help to provide a better understanding of the function of epigenetics regulation in adult stem cell differentiation.
Journal ArticleDOI
Co-motif discovery identifies an Esrrb-Sox2-DNA ternary complex as a mediator of transcriptional differences between mouse embryonic and epiblast stem cells.
Andrew P. Hutchins,Siew Hua Choo,Tapan Kumar Mistri,Tapan Kumar Mistri,Mehran Rahmani,Mehran Rahmani,Chow Thai Woon,Calista Keow Leng Ng,Calista Keow Leng Ng,Ralf Jauch,Paul Robson,Paul Robson +11 more
TL;DR: It is argued that the Esrrb‐Sox2 complex is an arbiter of gene expression differences between ESCs and epiblast stem cells (EpiSC) and the same trio may also function to maintain trophoblast stem cells.
Journal ArticleDOI
Very small embryonic-like cells: Biology and function of these potential endogenous pluripotent stem cells in adult tissues
TL;DR: Very small embryonic‐like cells (VSELs), found in murine bone marrow and other adult tissues, are small, non‐hematopoietic cells expressing markers of pluripotent embryonic and primordial germ cells, though a similar cell type in humans has begun to be characterized, though with a slightly different phenotype and surface markers.
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.