Reprogramming articles within Nature

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  • 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

  • News |

    Researchers have worked out how to reprogram cells from human skin into functioning nerve cells.

    • Ewen Callaway

  • News |

    Researchers are making inroads in the daunting challenge of modelling mental illness, thanks to patients' cells.

    • Ewen Callaway

  • Article |

    Reprogramming of somatic cells to induced pluripotent stem (iPS) cells that can be differentiated into many cell types has great potential for personalized therapy. By comparing copy number variations of early- and intermediate-passage human iPS cells to their respective parental fibroblast cells and human embryonic stem (ES) cells, this study finds that a high mutation rate is associated with the reprogramming process. However, during moderate length culture, human iPS cells undergo a selection process leading to decreased mutation load of cells equivalent to that observed in human ES cells.

    • Samer M. Hussein
    • , Nizar N. Batada
    •  & Timo Otonkoski

  • Article |

    Reprogramming of somatic cells to induced pluripotent stem (iPS) cells that can be differentiated into many cell types has great potential for personalized therapy. This study finds that 22 human iPS cell lines that were reprogrammed using five different methods contain protein coding point mutations. Some mutations were pre existing in the somatic cells, others were new mutations that occurred during and after reprogramming. Therefore, it will be important to ensure iPS cell safety before clinical use.

    • Athurva Gore
    • , Zhe Li
    •  & Kun Zhang

  • Letter |

    Reprogramming of X-chromosome inactivation during the acquisition of pluripotency is accompanied by repression of Xist, the trigger of X-inactivation, and by upregulation of its antisense counterpart, Tsix. In undifferentiated embryonic stem cells (ESCs), key transcription factors that support pluripotency repress Xist transcription. These authors show that upregulation of Tsix in ESCs depends on a different subset of pluripotency factors. Therefore, two distinct ESC-specific complexes couple reprogramming of X-inactivation to pluripotency.

    • Pablo Navarro
    • , Andrew Oldfield
    •  & Philip Avner

  • News & Views |

    Methods for generating embryonic-like stem cells have been established. The focus now is on finding ways to coax these cells into matching their natural counterparts as closely as possible, should this be desired.

    • Thomas P. Zwaka

  • Letter |

    The thymus contains thymic epithelial cells (TECs), which form a complex three-dimensional network organized into cortical and medullary compartments. It is shown here that these cells are plastic. Clonogenic TECs can acquire new properties when exposed to the skin microenvironment; under such conditions, they can permanently adopt the fate of hair follicle multipotent stem cells. Hence, microenvironmental cues can be sufficient to re-direct epithelial cell fate.

    • Paola Bonfanti
    • , Stéphanie Claudinot
    •  & Yann Barrandon

  • Article |

    Pluripotent stem cells can be generated in the laboratory through somatic cell nuclear transfer (generating nuclear transfer embryonic stem cells, ntESCs) or transcription-factor-based reprogramming (producing induced pluripotent stem cells, iPSCs). These methods reset the methylation signature of the genome — but to what extent? Here it is found that mouse iPSCs 'remember' the methylation status of their tissue of origin, but the methylation of ntESCs is more similar to that of naturally produced ES cells.

    • K. Kim
    • , A. Doi
    •  & G. Q. Daley

  • Article |

    Prevailing models propose that coronary arteries in the developing heart are formed from progenitor cells originating in the proepicardium. It is found here, however, that these arteries arise from angiogenic sprouts of the major vein that returns circulating blood to the embryonic heart. Thus some differentiated venous cells retain developmental plasticity and respond to local signals to convert to coronary arteries, capillaries and veins.

    • Kristy Red-Horse
    • , Hiroo Ueno
    •  & Mark A. Krasnow

  • News & Views |

    Ever since Leonardo da Vinci sketched the heart vessels in his anatomical notebook in the late fifteenth century, the origin of the coronary vasculature has been in question. We might just have come upon the answer.

    • Paul Riley

  • News & Views |

    In a feat of biological wizardry, one type of differentiated cell has been directly converted into another, completely distinct type. Notably, the approach does not require a stem-cell intermediate stage.

    • Cory R. Nicholas
    •  & Arnold R. Kriegstein

  • Letter |

    Here, iPS cell technology is used to study the mechanisms underlying dyskeratosis congenita in humans. Reprogramming restores telomere elongation in dyskeratosis congenita cells despite genetic lesions affecting telomerase. The reprogrammed cells were able to overcome a critical limitation in telomerase RNA component (TERC) levels to restore telomere maintenance and self-renewal, and multiple telomerase components are targeted by pluripotency-associated transcription factors.

    • Suneet Agarwal
    • , Yuin-Han Loh
    •  & George Q. Daley

  • Letter |

    The transcription factor Tbx3 is shown to significantly improve the quality of induced pluripotent stem (iPS) cells. Tbx3 binding sites in embryonic stem cells are present in genes involved in pluripotency and reprogramming factors. Furthermore, there are intrinsic qualitative differences in iPS cells generated by different methods in terms of their pluripotency, thus highlighting the need to rigorously characterize iPS cells beyond in vitro studies.

    • Jianyong Han
    • , Ping Yuan
    •  & Bing Lim

  • Letter |

    The extent of epigenetic reprogramming in mammalian primordial germ cells (PGCs) and in early embryos, and its molecular mechanisms, are poorly understood. DNA methylation profiling in PGCs now reveals a genome–wide erasure of methylation, with female PGCs being less methylated than male ones. A deficiency of the cytidine deaminase AID interferes with the genome–wide erasure of DNA methylation, indicating that AID has a critical function in epigenetic reprogramming.

    • Christian Popp
    • , Wendy Dean
    •  & Wolf Reik

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