Stem cells articles within Nature

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  • 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 |

    Little is known about how nutritional cues are detected by quiescent neural stem cells (neuroblasts in Drosophila melanogaster) and how these signals are relayed to reactivate their cell cycle to exit quiescence. This study uses an integrative physiology approach to identify the relay mechanism regulating this nutritional checkpoint in neural progenitors. It is found that specific insulin-like peptides produced within the brain by glia bridge the amino-acid/TOR-dependent signal derived from the fat body with PI3K/TOR signalling in neuroblasts to induce exit from quiescent.

    • Rita Sousa-Nunes
    • , Lih Ling Yee
    •  & Alex P. Gould

  • Letter |

    A common stem cell is known to produce both neural plate and mesoderm, but the factors regulating this choice are unknown. This study determines that Tbx6-dependent modulation of the developmental transcription factor Sox2 drives the fate of axial stem cells. In the absence of Tbx6, cells aberrantly upregulated Sox2 activity, with the result that cells originally destined to be mesoderm turned into ectopic neural tubes. In the absence of the N1 enhancer, this aberrant regulation is corrected and cells follow the appropriate fate, even in the absence of Tbx6. Therefore, active repression of the neural fate program is essential for mesoderm tissue to develop from axial stem cells.

    • Tatsuya Takemoto
    • , Masanori Uchikawa
    •  & Hisato Kondoh

  • Letter |

    Identifying the genomic regulatory sequences, such as enhancers, that control early embryonic development remains a difficult challenge. Here, profiling of histone modifications and chromatin regulators in human embryonic stem cells (hESCs) reveals unique signatures that are used to identify over 2,000 putative enhancers. These enhancers are either active in the h ESCs or associated with early developmental genes.

    • Alvaro Rada-Iglesias
    • , Ruchi Bajpai
    •  & Joanna Wysocka

  • Letter |

    Using a temporal series of growth factor manipulations to mimic embryonic intestinal development in culture, this study has successfully directed the differentiation of human pluripotent stem cells (both embryonic stem cells and induced pluripotent stem cells) into intestinal tissue. This approach may provide therapeutic benefit for disease studies.

    • Jason R. Spence
    • , Christopher N. Mayhew
    •  & James M. Wells

  • News |

    Replacing genes with drugs could allow safe reprogramming.

    • Ewen Callaway

  • News & Views |

    Tumour stem cells are proposed to be the source of tumour cells. It now emerges that they also give rise to the endothelial cells that line the tumour vasculature, mediating tumour growth and metastasis. See Letters p.824 & p.829

    • Victoria L. Bautch

  • News & Views |

    Blood cells are generated from haematopoietic stem cells on demand. The protein Lkb1, which lies at the crossroad of energy metabolism and cell growth, seems to regulate these stem cells' dynamics. See Articles p.653, p.659 & Letter p.701

    • Ellen M. Durand
    •  & Leonard I. Zon

  • Letter |

    Haematopoietic stem cells (HSCs) are very sensitive to energetic and oxidative stress, and modulation of the balance between their quiescence and proliferation is needed to respond to metabolic stress while preserving HSCs' long-term regenerative capacity. Here, and in two accompanying studies, it is shown that the tumour suppressor Lkb1 has a crucial role in maintaining energy homeostasis in haematopoietic cells.

    • Boyi Gan
    • , Jian Hu
    •  & Ronald A. DePinho

  • Article |

    Haematopoietic stem cells (HSCs) are very sensitive to energetic and oxidative stress, and modulation of the balance between their quiescence and proliferation is needed to respond to metabolic stress while preserving HSCs' long-term regenerative capacity. Here the tumour suppressor Lkb1 is shown to promote stem-cell maintenance and tissue regeneration by regulating energy metabolism and by preventing aneuploidy.

    • Daisuke Nakada
    • , Thomas L. Saunders
    •  & Sean J. Morrison

  • Article |

    Haematopoietic stem cells (HSCs) are very sensitive to energetic and oxidative stress, and modulation of the balance between their quiescence and proliferation is needed to respond to metabolic stress while preserving HSCs' long term regenerative capacity. Here the tumour suppressor Lkb1 is shown to have a crucial role in maintaining energy homeostasis in haematopoietic cells — an effect largely independent of AMPK and mTOR signalling.

    • Sushma Gurumurthy
    • , Stephanie Z. Xie
    •  & Nabeel Bardeesy

  • Letter |

    Multipotent stem cells expressing Lgr5 are known to generate all cell types of the intestinal epithelium (enterocytes, goblet cells, Paneth cells and enteroendocrine cells). A new study shows that Paneth cells have an essential role for intestinal crypt and stem cell maintenance by supplying essential niche signals to the Lgr5-expressing cells.

    • Toshiro Sato
    • , Johan H. van Es
    •  & Hans Clevers

  • Letter |

    Here it is shown that reactivation of endogenous telomerase activity in mice extends telomeres, reduces DNA damage signalling, allows resumption of proliferation in quiescent cultures, and eliminates degenerative phenotypes across multiple organs including testes, spleens and intestines. Accumulating evidence implicating telomere damage as a driver of age-associated organ decline and disease and the reversal of damage observed here support the development of regenerative strategies designed to restore telomere integrity.

    • Mariela Jaskelioff
    • , Florian L. Muller
    •  & Ronald A. DePinho

  • News & Views |

    Mobile DNA sequences called L1 contribute to the brain's genetic heterogeneity and may affect neuron function. The protein MeCP2, which is mutated in Rett syndrome, seems to regulate the activity of these genomic elements. See Letter p.443

    • Lorenz Studer

  • 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

  • Letter |

    These authors describe a molecular pathway by which endothelial cells sustain liver regeneration after surgical resection. Activation of vascular endothelial growth factor-A receptor-2 in a defined subpopulation of liver endothelial cells leads to the upregulation of the endothelial-specific transcription factor Id1, which in turn induces Wnt2 and hepatocyte growth factor, which are secreted from the endothelial cells and trigger hepatocyte proliferation.

    • Bi-Sen Ding
    • , Daniel J. Nolan
    •  & Shahin Rafii

  • Article |

    Mouse fibroblasts expressing a small subset of transcription factors can be induced to differentiate towards specified lineages without reverting to an embryonic state. Now direct conversion of dermal fibroblasts to multipotent blood progenitors has been achieved in vitro in the human, using just one factor.

    • Eva Szabo
    • , Shravanti Rampalli
    •  & Mickie Bhatia

  • News & Views |

    Stem cells can renew themselves indefinitely — a feature that is often attributed to asymmetrical cell division. Fresh experimental and mathematical models of the intestine provide evidence that begs to differ.

    • Michael P. Verzi
    •  & Ramesh A. Shivdasani

  • Letter |

    Two forms of X-chromosome inactivation ensure the selective silencing of female sex chromosomes in mouse embryos. Imprinted silencing begins with the detection of Xist RNA expression on the paternal X chromosome at about the four-cell stage of development. Later, a random form of inactivation silences either the paternal or the maternal X chromosome. Here it is shown that maternal deposits of the ubiquitin ligase Rnf12/RLIM are required for the imprinted form of X-chromosome inactivation.

    • JongDae Shin
    • , Michael Bossenz
    •  & Ingolf Bach

  • Letter |

    Realizing the full potential of human embryonic stem cells (hESCs) in research and clinical applications requires a detailed understanding of the genetic network that governs their unique properties. A genome-wide RNA interference screen identifies a wealth of new regulators of self-renewal and pluripotency properties in hESCs. The transcription factor PRDM14, for example, is required for the maintenance of hESC identity and reprogramming of somatic cells to pluripotency.

    • Na-Yu Chia
    • , Yun-Shen Chan
    •  & Huck-Hui Ng

  • News & Views |

    Enhancer sequences increase gene transcription with the help of a co-activator complex, the Mediator. Another protein complex — cohesin — seems to work with Mediator to bring together enhancers and promoters. See Article p. 430

    • Rolf Ohlsson

  • Books & Arts |

    Two books on ageing understate the challenges of prolonging a healthy lifespan, finds Caleb Finch.

    • Caleb Finch

  • 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

  • Brief Communications Arising |

    • Sanjay K. Singh
    • , Mohamedi N. Kagalwala
    •  & Sadhan Majumder

  • Article |

    Neurons of the peripheral nervous system need survival factors to prevent their death during development. Most in the central nervous system do not. Why are peripheral neurons so needy? Here it is shown that the neurotrophin receptors TrkA and TrkC, expressed at high levels by many peripheral nervous system neurons, behave as dependence receptors: they instruct neurons to die if there is no ligand around. By contrast, TrkB, expressed mainly in the central nervous system, does not signal death in the absence of ligand.

    • Vassiliki Nikoletopoulou
    • , Heiko Lickert
    •  & Yves-Alain Barde

  • Editorial |

    Congress must act quickly to save US stem-cell research.

  • Letter |

    TET1 is an enzyme that catalyses the conversion of 5-methylcytosine of DNA to 5-hydroxymethylcytosine, raising the possibility that it is involved in mediating DNA demethylation. These authors show that Tet1 is involved in mouse embryonic stem cell maintenance and specification of the inner cell mass. It is required to maintain both the expression of Nanog in embryonic stem cells and the Nanog promoter in a hypomethylated state, supporting a role for Tet1 in regulating DNA methylation.

    • Shinsuke Ito
    • , Ana C. D’Alessio
    •  & Yi Zhang

  • Technology Feature |

    Long-term, live-cell imaging helps to settle long-running debates. Monya Baker investigates how the huge investment and time commitment is finally paying off.

    • Monya Baker

  • 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 |

    Gene activation may involve the formation of a DNA loop that connects enhancer-bound transcription factors with the transcription apparatus at the core promoter. But this process is not well understood. Here, two proteins, mediator and cohesin, are shown to connect the enhancers and core promoters of active genes in embryonic stem cells. These proteins seem to generate cell-type-specific DNA loops linked to the gene expression program of each cell.

    • Michael H. Kagey
    • , Jamie J. Newman
    •  & Richard A. Young

  • Letter |

    During haematopoiesis, multipotent progenitors differentiate into progressively restricted myeloid or lymphoid progenitors. A comprehensive genome-wide DNA methylation analysis of haematopoietic cell populations with well-characterized differentiation potentials reveals remarkable epigenetic plasticity during lymphoid and myeloid restriction.

    • Hong Ji
    • , Lauren I. R. Ehrlich
    •  & Andrew P. Feinberg

  • Article |

    The identity of the cells that form the haematopoietic stem cell (HSC) niche in bone marrow has been unclear. These authors identify nestin-expressing mesenchymal stem cells as niche-forming cells. These nestin-expressing cells show a close physical association with HSCs and express high levels of genes involved in HSC maintenance, and their depletion reduces bone marrow homing of haematopoietic progenitors.

    • Simón Méndez-Ferrer
    • , Tatyana V. Michurina
    •  & Paul S. Frenette

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