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
The nature of embryonic stem cells.
Graziano Martello,Austin Smith +1 more
TL;DR: The authenticity of ES cells in relation to cells in the embryo is evaluated and their utility for dissecting mechanisms that confer pluripotency are examined, including the challenge of deriving ground state pluripotent stem cells from non-rodent species.
Journal ArticleDOI
Metastable Pluripotent States in NOD-Mouse-Derived ESCs
Jacob H. Hanna,Styliani Markoulaki,Maisam Mitalipova,Albert W. Cheng,John P. Cassady,Judith Staerk,Bryce W. Carey,Christopher J. Lengner,Ruth K. Foreman,Jennifer M. Love,Qing Gao,Jongpil Kim,Rudolf Jaenisch +12 more
TL;DR: It is found that NOD stem cells can be stabilized by providing constitutive expression of Klf4 or c-Myc or small molecules that can replace these factors during in vitro reprogramming, which suggests that stem cells from different genetic backgrounds can assume distinct states of pluripotency in vitro.
Journal ArticleDOI
Induced Pluripotent Stem Cells Meet Genome Editing
Dirk Hockemeyer,Rudolf Jaenisch +1 more
TL;DR: How two such experiments-the generation of human induced pluripotent stem cells (iPSCs) and the development of CRISPR/Cas9 technology-have fundamentally reshaped the approach to biomedical research, stem cell biology, and human genetics is reviewed.
Journal ArticleDOI
Derivation of Pluripotent Stem Cells with In Vivo Embryonic and Extraembryonic Potency
Yang Yang,Bei Liu,Jun Xu,Jinlin Wang,Jun Wu,Cheng Shi,Yaxing Xu,Jiebin Dong,Chengyan Wang,Weifeng Lai,Jialiang Zhu,Liang Xiong,Dicong Zhu,Xiang Li,Weifeng Yang,Takayoshi Yamauchi,Atsushi Sugawara,Zhongwei Li,Fangyuan Sun,Xiangyun Li,Li Chen,Aibin He,Yaqin Du,Ting Wang,Chaoran Zhao,Haibo Li,Xiaochun Chi,Hongquan Zhang,Yifang Liu,Cheng Li,Shuguang Duo,Ming Yin,Huan Shen,Juan Carlos Izpisua Belmonte,Hongkui Deng +34 more
TL;DR: It is shown that a chemical cocktail enables the derivation of stem cells with unique functional and molecular features from mice and humans, designated as extended pluripotent stem (EPS) cells, which are capable of chimerizing both embryonic and extraembryonic tissues.
Journal ArticleDOI
Deconstructing transcriptional heterogeneity in pluripotent stem cells
Roshan M. Kumar,Patrick Cahan,Alex K. Shalek,Rahul Satija,AJay DaleyKeyser,Hu Li,Jin Zhang,Keith Pardee,Keith Pardee,David Gennert,John J. Trombetta,Thomas C. Ferrante,Aviv Regev,Aviv Regev,George Q. Daley,James J. Collins,James J. Collins +16 more
TL;DR: In this paper, the authors characterize transcriptional heterogeneity in Pluripotent Stem Cells (PSCs) by single-cell single-input single-out (SISO) experiments.
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.