Embryonic stem cells

  • Article |

    Depletion of TRF2—an essential mediator of telomere protection in most mammalian cells—in mouse embryonic stem cells activates a compensatory transcriptional program that renders TRF2 dispensable for their survival and proliferation.

    • Marta Markiewicz-Potoczny
    • , Anastasia Lobanova
    •  & Eros Lazzerini Denchi
  • Article |

    Single-cell RNA sequencing and spatial transcriptomics reveal that the somitogenesis clock is active in mouse gastruloids, which can be induced to generate somites with the correct rostral–caudal patterning.

    • Susanne C. van den Brink
    • , Anna Alemany
    •  & Alexander van Oudenaarden
  • Article |

    ERK reversibly regulates embryonic stem cell transcription via selective redistribution of co-factors and RNA polymerase from pluripotency to early differentiation enhancers, while leaving transcription factors bound to their enhancers, thus preserving plasticity.

    • William B. Hamilton
    • , Yaron Mosesson
    •  & Joshua M. Brickman
  • Letter |

    The transcription factor OTX2 ensures that germline induction is initially kept in check and only proceeds after OTX2 downregulation.

    • Jingchao Zhang
    • , Man Zhang
    •  & Ian Chambers
  • Letter |

    Stimulation of Wnt and Nodal pathways in micropatterned human embryonic stem cell colonies induce these colonies to exhibit characteristic spatial expression patterns of the organizer and reproduce organizer function when grafted into a host embryo.

    • I. Martyn
    • , T. Y. Kanno
    •  & A. H. Brivanlou
  • Letter |

    Trophoblast and embryonic stem cells interact in vitro to form structures that resemble early blastocysts, and the embryo provides signals that drive early trophectoderm development and implantation.

    • Nicolas C. Rivron
    • , Javier Frias-Aldeguer
    •  & Niels Geijsen
  • Letter |

    Exit of epiblasts from an unrestricted naive pluripotent state is required for epithelialization and generation of the pro-amniotic cavity in mouse embryos and for amniotic cavity formation in human embryos and human embryonic stem cells.

    • Marta N. Shahbazi
    • , Antonio Scialdone
    •  & Magdalena Zernicka-Goetz
  • Letter |

    Cultures of expanded potential stem cells can be established from individual eight-cell blastomeres, and by direct conversion of mouse embryonic stem cells and induced pluripotent stem cells, highlighting the feasibility of establishing expanded potential stem cells for other mammalian species.

    • Jian Yang
    • , David J. Ryan
    •  & Pentao Liu
  • Letter |

    The authors surveyed whole-exome and RNA-sequencing data from 252 unique pluripotent stem cell lines, some of which are in the pipeline for clinical use, and found that approximately 5% of cell lines had acquired mutations in the TP53 gene that allow mutant cells to rapidly outcompete non-mutant cells, but do not prevent differentiation.

    • Florian T. Merkle
    • , Sulagna Ghosh
    •  & Kevin Eggan
  • Article |

    A technique called genome architecture mapping (GAM) involves sequencing DNA from a large number of thin nuclear cryosections to develop a map of genome organization without the limitations of existing 3C-based methods.

    • Robert A. Beagrie
    • , Antonio Scialdone
    •  & Ana Pombo
  • Letter |

    Inhibition of mechanistic target of rapamycin (mTOR) suspends mouse blastocyst development and the cells remain ‘paused’ in a reversible pluripotent state, allowing prolonged culture.

    • Aydan Bulut-Karslioglu
    • , Steffen Biechele
    •  & Miguel Ramalho-Santos
  • Letter |

    Using a protocol that recapitulates both meiosis and oocyte growth in vitro, the authors induce mouse pluripotent stem cells to differentiate into fully functional oocytes that can be fertilized and generate viable offspring, thereby recapitulating the full mammalian female germline cycle in a dish.

    • Orie Hikabe
    • , Nobuhiko Hamazaki
    •  & Katsuhiko Hayashi
  • Article |

    The prevalence of N6-adenine DNA methylation in mammals was previously unknown; this study reveals that N6-methyladenine can be found in mouse embryonic stem cells, especially at subfamilies of young (<1.5 million years old) LINE-1 transposons.

    • Tao P. Wu
    • , Tao Wang
    •  & Andrew Z. Xiao
  • Letter |

    Haploid human embryonic stem cells have been derived from haploid oocytes, the cells maintain a normal haploid karyotype as pluripotent cells and, unexpectedly, as differentiated cells — loss-of-function genetic screens previously performed with haploid embryonic stem cells in mice can now be performed in humans.

    • Ido Sagi
    • , Gloryn Chia
    •  & Nissim Benvenisty
  • Letter |

    A differentiation protocol to obtain enteric nervous system (ENS) progenitors and a range of neurons from human pluripotent stem cells is developed; the cells can migrate and graft to the colon of a chick embryo and an adult mouse colon, including in a mouse model of Hirschsprung disease, in which a functional rescue is observed.

    • Faranak Fattahi
    • , Julius A Steinbeck
    •  & Lorenz Studer
  • Review Article |

    In response to the need for a defined set of criteria to assess stem-cell potency, this review proposes guidelines for the evaluation of newly derived pluripotent stem cells, from functional assays to integrative molecular analyses of transcriptional, epigenetic and metabolic states.

    • Alejandro De Los Angeles
    • , Francesco Ferrari
    •  & George Q. Daley
  • Letter |

    This study shows that a vertebrate-specific ubiquitin ligase modulates neural crest specification in Xenopus development and human embryonic stem-cell differentiation; a proteomics approach reveals that the CUL3KBTBD8 ligase modulates translation by targeting the modulators of ribosomes production NOLC1 and its paralogue TCOF1, which is mutated in a neural-crest-associated syndrome.

    • Achim Werner
    • , Shintaro Iwasaki
    •  & Michael Rape
  • Article
    | Open Access

    An analysis of genome-wide chromatin interactions during human embryonic stem cell differentiation reveals changes in chromatic organization and simultaneously identifies allele-resolved chromatin structure and differences in gene expression during differentiation.

    • Jesse R. Dixon
    • , Inkyung Jung
    •  & Bing Ren
  • Article |

    This study uses single-cell expression profiling of pluripotent stem cells after various perturbations, and uncovers a high degree of variability that can be inherited through cell divisions—modulating microRNA or external signalling pathways induces a ground state with reduced gene expression heterogeneity and a distinct chromatin profile.

    • Roshan M. Kumar
    • , Patrick Cahan
    •  & James J. Collins
  • Letter |

    The in vitro generation, from pluripotent stem cells, of three-dimensional human gastric organoids (hGOs) that contain a physiological gastric epithelium comprising both progenitor and differentiated cell types, and have expected functional characteristics is described, as is modelling the pathophysiological response of the human stomach to Helicobacter pylori using these hGOs.

    • Kyle W. McCracken
    • , Emily M. Catá
    •  & James M. Wells
  • Letter |

    The structure of mouse Dis3l2 bound to an oligoU substrate shows a funnel-like substrate-binding site with the RNA being fed into the active site along a path that is distinct from that seen in the related catalytic subunit of the exosome — 12 uracils of the oligoU-tailed RNA are recognized in a complex network of interactions, suggesting the basis for target specificity.

    • Christopher R. Faehnle
    • , Jack Walleshauser
    •  & Leemor Joshua-Tor
  • Letter |

    The ubiquitin ligase RLIM is known to activate the long non-coding RNA Xist, which is crucial for X-chromosome inactivation in female mice; however, unlike imprinted X-chromosome inactivation that requires RLIM for Xist expression, evidence is now provided that during random X-chromosome inactivation Xist expression is regulated by an RLIM-independent pathway in vivo.

    • JongDae Shin
    • , Mary C. Wallingford
    •  & Ingolf Bach
  • Letter |

    Regeneration of the heart muscle after myocardial infarction with cardiomyocytes derived from human embryonic stem cells is demonstrated in non-human primates, with the grafts showing evidence of electromechanical coupling, although they were also associated with non-fatal arrhythmias.

    • James J. H. Chong
    • , Xiulan Yang
    •  & Charles E. Murry
  • Letter |

    It is known that human embryonic stem (ES) cells are more similar to mouse primed epiblast stem cells than to naive mouse ES cells; here culture conditions are determined that allow human ES and induced pluripotent stem cells to acquire a pluripotent state that retains growth characteristics highly similar to mouse naive ES cells, and competence in generating cross-species human-mouse embryonic chimaerism.

    • Ohad Gafni
    • , Leehee Weinberger
    •  & Jacob H. Hanna
  • Article |

    This study shows that the combination of naive pluripotency growth conditions, Oct4, Sox2, Klf4 and Myc (OSKM) overexpression, and depleting the Mbd3/NuRD co-repressor results in deterministic and synchronized reprogramming to pluripotency.

    • Yoach Rais
    • , Asaf Zviran
    •  & Jacob H. Hanna
  • Letter |

    A new approach has been developed in order to achieve the stepwise differentiation of inner ear sensory epithelia from mouse embryonic stem cells in a three-dimensional culture: this process, which mimics normal development and produces cells that have functional characteristics of mechanosensitive hair cells, is hoped to provide further insights into inner ear development and disorder.

    • Karl R. Koehler
    • , Andrew M. Mikosz
    •  & Eri Hashino
  • Article |

    An in vivo genetic approach to generate mosaic expression of Myc in the mouse epiblast reveals evidence of cell competition, a tissue homeostasis mechanism first described in Drosophila by which viable but suboptimal cells are eliminated from metazoan tissues; during normal development Myc expression levels in the epiblast are heterogeneous, and endogenous cell competition refines the epiblast cell population through the apoptotic elimination of cells with low relative Myc levels.

    • Cristina Clavería
    • , Giovanna Giovinazzo
    •  & Miguel Torres
  • Letter |

    Vitamin C is a direct regulator of Tet enzyme activity and DNA methylation fidelity in mouse ES cells; addition of vitamin C promotes Tet activity, increases 5-hydroxymethlycytosine (5hmC) and DNA demethylation of many gene promoters, upregulates demethylated germline genes, and induces a state that more closely approximates that of the inner cell mass of the blastocyst.

    • Kathryn Blaschke
    • , Kevin T. Ebata
    •  & Miguel Ramalho-Santos
  • Letter |

    This study shows that Dis3l2 is the 3′–5′ exonuclease that mediates the degradation of uridylated precursor let-7 microRNA; this is the first physiological RNA substrate identified for this new exonuclease, which causes the Perlman syndrome of fetal overgrowth and Wilms’ tumour susceptibility when mutated.

    • Hao-Ming Chang
    • , Robinson Triboulet
    •  & Richard I. Gregory
  • Letter |

    Mouse androgenetic haploid embryonic stem cell lines can be established by transferring sperm into an enucleated oocyte; the cells maintain haploidy and stable growth over 30 passages, express pluripotent markers, are able to differentiate into all three germ layers, contribute to germlines of chimaeras when injected into blastocysts and can produce fertile progeny that carry genetic modifications to the next generation.

    • Wei Li
    • , Ling Shuai
    •  & Qi Zhou
  • Letter |

    Two types of human ES-cell-derived otic progenitors are shown to have the ability to differentiate in vitro into hair-cell-like cells and auditory neurons, and to engraft, differentiate and improve auditory-evoked response thresholds when transplanted into an auditory neuropathy model; this indicates that it may be possible to use cell-based therapeutic strategies to recover damaged sensory circuitry in deafness.

    • Wei Chen
    • , Nopporn Jongkamonwiwat
    •  & Marcelo N. Rivolta