Reprogramming

  • Article |

    Expression of three Yamanaka transcription factors in mouse retinal ganglion cells restores youthful DNA methylation patterns, promotes axon regeneration after injury, and reverses vision loss in a mouse model of glaucoma and in aged mice, suggesting that mammalian tissues retain a record of youthful epigenetic information that can be accessed to improve tissue function.

    • Yuancheng Lu
    • , Benedikt Brommer
    •  & David A. Sinclair
  • Article |

    A set of five small molecules can induce the transformation of fibroblasts into rod photoreceptor-like cells, which can partially restore pupil reflex and visual function when transplanted into a rod degeneration mouse model.

    • Biraj Mahato
    • , Koray Dogan Kaya
    •  & Sai H. Chavala
  • Article |

    Combinatorial tagging of single cells using expressed DNA barcodes, delivered by a lentiviral vector, is used to track individual cells and reconstruct their lineages and trajectories during cell fate reprogramming.

    • Brent A. Biddy
    • , Wenjun Kong
    •  & Samantha A. Morris
  • Letter |

    Gonadal germline epigenetic reprogramming involves an interplay between DNA methylation, the polycomb complex and Tet1 in both DNA methylation dependent and independent roles, to ensure the activation of a specific subset of genes critical for progression of gametogenesis.

    • Peter W. S. Hill
    • , Harry G. Leitch
    •  & Petra Hajkova
  • Letter |

    Three papers in this issue of Nature use highly sensitive ChIP–seq assays to describe the dynamic patterns of histone modifications during early mouse embryogenesis, showing that oocytes have a distinctive epigenome and providing insights into how the maternal gene expression program transitions to the zygotic program.

    • John Arne Dahl
    • , Inkyung Jung
    •  & Arne Klungland
  • Letter |

    A human neurodevelopmental model fills the current knowledge gap in the cellular biology of Williams syndrome and could lead to further insights into the molecular mechanism underlying the disorder and the human social brain.

    • Thanathom Chailangkarn
    • , Cleber A. Trujillo
    •  & Alysson R. Muotri
  • Letter |

    The transcriptome changes driving the conversion of fibroblasts to neurons at the single-cell level are reported, revealing that early neuronal reprogramming steps are homogenous, driven by the proneural pioneer factor Ascl1; the expression of myogenic genes then has a dampening effect on efficiency, which needs to be counteracted by the neuronal factors Myt1l and Brn2 for more efficient reprogramming.

    • Barbara Treutlein
    • , Qian Yi Lee
    •  & Stephen R. Quake
  • 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
  • Letter |

    Inhibitory antibodies to two specific human and mouse Notch ligands, Jagged1 and Jagged2, are generated and shown to have beneficial effects in a goblet cell metaplasia asthma model; systemic Jagged1 inhibition transdifferentiates secretory cells into ciliated cells in the mouse, demonstrating that Jagged1 from ciliated cells normally holds back secretory cells to adopt the ciliated fate.

    • Daniel Lafkas
    • , Amy Shelton
    •  & Christian W. Siebel
  • Article |

    The forced expression of key transcription factors can induce somatic cells to acquire pluripotency characteristics; here high levels of reprogramming factors are used to induce mouse embryonic fibroblasts to a stable alternative pluripotent state with low intercellular adhesion.

    • Peter D. Tonge
    • , Andrew J. Corso
    •  & Andras Nagy
  • Letter |

    The Arabidopsis thaliana floral repressor FLC is epigenetically silenced by prolonged cold in a process called vernalization and then is reactivated before the completion of seed development; a histone demethylase, ELF6, is now shown to be involved in reactivating FLC in reproductive tissues, allowing the resetting of FLC expression and thus the requirement for vernalization in each generation.

    • Pedro Crevillén
    • , Hongchun Yang
    •  & Caroline Dean
  • Letter |

    Base-resolution maps of DNA methylation in human gametes and early embryos offer novel insights into human methylation dynamics and the functional relationship between DNA methylation and gene expression.

    • Hongshan Guo
    • , Ping Zhu
    •  & Jie Qiao
  • Article |

    This study describes the conversion of human fetal and adult vascular endothelial cells into engraftable haematopoietic progenitors by transduction with some transcription factors and then culture on a vascular niche feeder layer; the haematopoietic progenitors may be useful for the generation of engraftable healthy and long-lasting haematopoietic cells for treatment of inherited and acquired blood disorders.

    • Vladislav M. Sandler
    • , Raphael Lis
    •  & Shahin Rafii
  • Letter |

    Reprogramming after somatic cell nuclear transfer had been thought to be dependent on the recipient cytoplasm being arrested at the metaphase stage, but here interphase two-cell mouse embryos are shown to support successful reprogramming and generation of embryonic stem cells or cloned mice.

    • Eunju Kang
    • , Guangming Wu
    •  & Shoukhrat Mitalipov
  • Article |

    One of two papers describing a reprogramming phenomenon called stimulus-triggered acquisition of pluripotency (STAP) — in STAP, lineage-committed adult somatic cells are reprogrammed to pluripotency by transient exposure to low-pH treatment, and extensive analysis of the molecular features and developmental potential of STAP cells indicates that they represent a unique state of pluripotency.

    • Haruko Obokata
    • , Teruhiko Wakayama
    •  & Charles A. Vacanti
  • Letter |

    This study shows that PADI4-mediated citrullination occurs during pluripotency and that citrullination of H1 results in loosening of chromatin compaction; furthermore, citrullination is shown to be important for the activation of stem-cell genes, for iPS cell reprogramming and to maintain pluripotent cells in the early mouse embryo.

    • Maria A. Christophorou
    • , Gonçalo Castelo-Branco
    •  & Tony Kouzarides
  • Letter |

    Generation of human induced pluripotent stem cells from patient fibroblasts containing ring chromosomes with large deletions reveals that reprogrammed cells lose the abnormal chromosome and duplicate the wild-type homologue through compensatory uniparental disomy, suggesting that cellular reprogramming may hold potential for ‘chromosome therapy’.

    • Marina Bershteyn
    • , Yohei Hayashi
    •  & Anthony Wynshaw-Boris
  • Article |

    Using in vivo lineage tracing in mice and sorted cells in culture, the ability of stably committed cells to dedifferentiate into basal stem cells in the mouse trachea is investigated: the findings suggest that the dedifferentiation of committed cell types into stem cells may contribute generally to regeneration in higher vertebrates in different organ and injury contexts.

    • Purushothama Rao Tata
    • , Hongmei Mou
    •  & Jayaraj Rajagopal
  • 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
  • Article |

    Induced pluripotent stem cells (iPS cells) have been created in vivo by reprogramming mouse somatic cells with Oct4, Sox2, Klf4 and c-Myc; these cells have totipotent features that are missing from in vitro created iPS cells or embryonic stem cells.

    • María Abad
    • , Lluc Mosteiro
    •  & Manuel Serrano
  • Letter |

    Cellular reprogramming is shown to occur in an ordered, stepwise manner, marked by changes in the cell-surface markers CD44, ICAM1 and Nanog–eGFP; molecular characterization of discrete subpopulations of partially reprogrammed cells shows that reprogramming is not simply the reversal of the normal development process.

    • James O’Malley
    • , Stavroula Skylaki
    •  & Keisuke Kaji
  • Article |

    A combination of four transcription factors, GATA4, HAND2, MEF2C and TBX5, can reprogram fibroblasts into cardiac-like myocytes in vitro and in vivo; expression of these factors ameliorated cardiac function in mice that had suffered myocardial infarction.

    • Kunhua Song
    • , Young-Jae Nam
    •  & Eric N. Olson
  • Article |

    Previous work has shown that a combination of three transcription factors can directly reprogram cardiac fibroblasts into cardiomyocyte-like cell in vitro; now, the same authors demonstrate in vivo reprogramming of cardiac fibroblasts into induced cardiomyocytes.

    • Li Qian
    • , Yu Huang
    •  & Deepak Srivastava
  • Letter |

    Inhibition of DOT1L, the H3K79 histone methyltransferase, increases cell reprogramming and substituted for KLF4 and c-Myc, showing that chromatin-modifying enzymes act not only as facilitators but also as barriers to reprogramming.

    • Tamer T. Onder
    • , Nergis Kara
    •  & George Q. Daley
  • Brief Communications Arising |

    • Yang-Yu Liu
    • , Jean-Jacques Slotine
    •  & Albert-László Barabási