Pluripotent stem cells

  • Article |

    The single-cell transcriptional profile of a human embryo between 16 and 19 days after fertilization reveals parallels and differences in gastrulation in humans as compared with mouse and non-human primate models.

    • Richard C. V. Tyser
    • , Elmir Mahammadov
    •  & Shankar Srinivas
  • Article |

    Primed pluripotent stem cells from distant species compete with each other, and inactivation of NF-κB signalling in normally outcompeted human cells improves their survival and chimerism in mouse embryos.

    • Canbin Zheng
    • , Yingying Hu
    •  & Jun Wu
  • Article |

    The authors show that metabolic activity leads to an increase in the intracellular pH of neuromesodermal precursors, and that this increase in pH, by allowing post-translational modification of β-catenin, is required for the activation of WNT signalling and mesodermal fate acquisition.

    • Masayuki Oginuma
    • , Yukiko Harima
    •  & Olivier Pourquié
  • Article |

    A system involving in vitro induction of presomitic mesoderm recapitulates oscillatory expression of core segmentation clock genes and travelling-wave-like gene expression, suggesting that this system can be used to study the human segmentation clock and provide insights into diseases associated with human axial skeletogenesis.

    • Mitsuhiro Matsuda
    • , Yoshihiro Yamanaka
    •  & Cantas Alev
  • 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 |

    Integrative analyses identify host proteins that are modulated by Zika virus at multiple levels and provide a comprehensive framework for the understanding of Zika virus-induced changes to cellular pathways.

    • Pietro Scaturro
    • , Alexey Stukalov
    •  & Andreas Pichlmair
  • 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 |

    A tissue culture system that provides an increasing intensity of electromechanical stimulation over time enables an in vitro model of cardiac tissue derived from human induced pluripotent stem cells to develop many of the characteristics of adult cardiac tissue.

    • Kacey Ronaldson-Bouchard
    • , Stephen P. Ma
    •  & Gordana Vunjak-Novakovic
  • Article |

    Using a single-cell sequencing analysis in monkey embryos, and comparing the genes expressed during early development in this species with those in mice and in human pluripotent stem cells, the authors define characteristics of pluripotency ontogeny across mammalian species.

    • Tomonori Nakamura
    • , Ikuhiro Okamoto
    •  & Mitinori Saitou
  • Letter |

    A CRISPR/Cas9 genome editing framework has been developed that allows controlled introduction of mono- and bi-allelic sequence changes, and is used to generate induced human pluripotent stem cells with heterozygous and homozygous dominant mutations in amyloid precursor protein and presenilin 1 that have been associated with early onset Alzheimer’s disease.

    • Dominik Paquet
    • , Dylan Kwart
    •  & Marc Tessier-Lavigne
  • 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 protocol has been developed to use human induced pluripotent stem cells to obtain a self-formed ectodermal autonomous multizone, which includes distinct cell lineages of the eye, including the ocular surface ectoderm, lens, neuro-retina, and retinal pigment epithelium that can be expanded to form a functional corneal epithelium when transplanted to an animal model of corneal visual impairment.

    • Ryuhei Hayashi
    • , Yuki Ishikawa
    •  & Kohji Nishida
  • 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
  • Letter |

    In mouse embryonic stem cells converted to an epiblast fate in vitro—a state in which the cells can also gain germ cell fate if exposed to the signalling molecule BMP4—the sole expression of the transcription factor NANOG is shown to be sufficient to induce germ cell fate, in the absence of BMP4.

    • Kazuhiro Murakami
    • , Ufuk Günesdogan
    •  & M. Azim Surani
  • Article |

    RNA interference screens were used to identify chromatin-associated factors that impede reprogramming of somatic cells into iPS cells; suppression of the chromatin assembly factor CAF-1 enhances the generation of iPS cells by rendering chromatin more accessible to pluripotency transcription factors.

    • Sihem Cheloufi
    • , Ulrich Elling
    •  & Konrad Hochedlinger
  • 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
  • Article |

    A previously unknown type of stem cell that can engraft in specific regions of the mouse epiblast is described; these region-selective pluripotent stem cells display notable intra- and inter-specific chimaera competency and will help to further our understanding of mammalian development.

    • Jun Wu
    • , Daiji Okamura
    •  & Juan Carlos Izpisua Belmonte
  • Article |

    This study presents an extensive molecular characterization of the reprograming process by analysis of transcriptomic, epigenomic and proteomic data sets describing the routes to pluripotency; it finds distinct routes towards two stable pluripotent states characterized by distinct epigenetic events.

    • Samer M. I. Hussein
    • , Mira C. Puri
    •  & Andras Nagy
  • 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
  • Article |

    This study reprograms fibroblasts from thanatophoric dysplasia type I (TD1) and achondroplasia (ACH) patients into induced pluripotent stem cells (iPSCs), finding that chondrogenic differentiation results in the formation of degraded cartilage; statin treatment led to significant recovery of bone growth in a mouse model of ACH.

    • Akihiro Yamashita
    • , Miho Morioka
    •  & Noriyuki Tsumaki
  • 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 |

    A pulse of C/EBPα followed by overexpression of the transcription factors Oct4, Sox2, Klf4 and Myc leads to fast and very efficient reprogramming of B cell precursors to induced pluripotent stem cells; C/EBPα facilitates transient chromatin accessibility and accelerates expression of pluripotency genes through a mechanism that involves activation of the Tet2 enzyme.

    • Bruno Di Stefano
    • , Jose Luis Sardina
    •  & Thomas Graf
  • 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
  • Letter |

    Induced pluripotent stem-cell characterization reveals phenotypical differences between humans and non-human primates (NHPs): gene expression analysis shows differences in the regulation of long interspersed element-1 (L1) transposons, and in the expression of L1-restricting genes APOBEC3B and PIWIL2, correlating with higher L1 mobility in NHPs; this indicates that L1 mobility differences may have differentially shaped the human and NHP genomes.

    • Maria C. N. Marchetto
    • , Iñigo Narvaiza
    •  & Fred H. Gage
  • 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 |

    Using 4C technology, higher-order topological features of the pluripotent genome are identified; in pluripotent stem cells, Nanog clusters specifically with other pluripotency genes and this clustering is centred around Nanog-binding sites, suggesting that Nanog helps to shape the three-dimensional structure of the pluripotent genome and thereby contributes to the robustness of the pluripotent state.

    • Elzo de Wit
    • , Britta A. M. Bouwman
    •  & Wouter de Laat
  • Letter |

    Vascularized, functional human liver is generated from human induced pluripotent stem cells (iPSCs) by transplantation of liver buds created in vitro (iPSC-LBs); hepatic cells self-organized into three-dimensional iPSC-LBs, and human vasculatures in iPSC-LB transplants became functional by connecting to host vessels, stimulating maturation of iPSC-LBs into tissue resembling adult liver and performing liver-specific functions.

    • Takanori Takebe
    • , Keisuke Sekine
    •  & Hideki Taniguchi
  • Letter |

    The authors show that the pluripotency factor NANOG interacts with TET1 and TET2 methylcytosine hydroxylases, and that the hydroxylation of 5-methylcytosine to 5-hydroxymethylcytosine enhances the efficiency of somatic cell reprogramming in a NANOG-dependent manner.

    • Yael Costa
    • , Junjun Ding
    •  & Jianlong Wang