Haematopoietic stem cells articles within Nature

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  • Article |

    On the basis of transplantation experiments it is generally believed that a very small number of haematopoietic stem cells maintain multi-lineage haematopoiesis by stably producing a hierarchy of short-lived progenitor cells; here a new transposon-based labelling technique shows that this might not be the case during non-transplant haematopoiesis, but rather that a large number of long-lived progenitors are the main drivers of steady-state haematopoiesis during most of adulthood.

    • Jianlong Sun
    • , Azucena Ramos
    •  & Fernando D. Camargo

  • Letter |

    A new somite compartment, called the endotome, that contributes to the formation of the embryonic dorsal aorta by providing endothelial progenitors is identified here; endotome-derived endothelial progenitors, whose formation is regulated by the activity of the meox1 gene, induce haematopoietic stem cell formation upon colonization of the nascent dorsal aorta.

    • Phong Dang Nguyen
    • , Georgina Elizabeth Hollway
    •  & Peter David Currie

  • Letter |

    Notch signalling has a key role in the generation of haematopoietic stem cells (HSCs) during vertebrate development; here two adhesion molecules, Jam1a and Jam2a, are shown to be essential for the contact between precursors of HSCs and the somite during embryonic migration, and the Jam1a–Jam2a interaction is shown to be needed to transmit the Notch signal and produce HSCs.

    • Isao Kobayashi
    • , Jingjing Kobayashi-Sun
    •  & David Traver

  • Letter |

    Haematopoietic stem cell (HSC) function is known to degrade with age; here, replication stress is shown to be a potent driver of the functional decline of HSCs during physiological ageing in mice due to decreased expression of mini-chromosome maintenance helicase components and reduced activity of the DNA replication machinery.

    • Johanna Flach
    • , Sietske T. Bakker
    •  & Emmanuelle Passegué

  • Letter |

    Molecular, pharmacological and functional data show that haematopoietic stem cells (HSCs) are predisposed to ER-stress-mediated apoptosis compared to closely related progenitors; a framework for understanding how stress signalling is coordinated within the hematopoietic hierarchy and integrated with stemness is provided, and may have implications for the improvement of clinical transplantation of HSCs.

    • Peter van Galen
    • , Antonija Kreso
    •  & John E. Dick

  • Article |

    Haematopoietic stem cells (HSCs) have a lower rate of protein synthesis in vivo than most other haematopoietic cells, and both increases and decreases in the rate of protein synthesis impair HSC function, demonstrating that HSC maintenance—and hence, cellular homeostasis—requires the rate of protein synthesis to be highly regulated.

    • Robert A. J. Signer
    • , Jeffrey A. Magee
    •  & Sean J. Morrison

  • Letter |

    Here, using two-photon phosphorescence lifetime microscopy, the local oxygen tension in the bone marrow of live mice is found to be quite low, with spatiotemporal variations depending on the blood vessel type, distance to the endosteum, and changes in cellularity after stress.

    • Joel A. Spencer
    • , Francesca Ferraro
    •  & Charles P. Lin

  • Letter |

    Haematopoietic stem cells are found to be regulated differently in male and female mice — haematopoietic stem cells in females divide more frequently than in males in response to oestrogen and this difference depends on the ovaries but not the testes; using a genetic approach, it is shown that the effect is dependent on expression of oestrogen receptor-α (ERα) in stem cells.

    • Daisuke Nakada
    • , Hideyuki Oguro
    •  & Sean J. Morrison

  • Letter |

    Oncogenic Nras in mouse haematopoietic stem cells can increase the probability of cell division in some cells and decrease it in others; this bimodal activity explains how this single pre-leukaemic mutation can increase proliferation without reducing competitiveness by clonally expanding the rapidly dividing cell population and also promoting long-term self-renewal of stem cells.

    • Qing Li
    • , Natacha Bohin
    •  & Sean J. Morrison

  • Letter |

    The identification of a functionally distinct subset of haematopoietic stem cells (HSCs) that is primed for platelet-specific gene expression is described; the cells frequently have long-term myeloid lineage bias, can self-renew and give rise to lymphoid-biased HSCs, and may enable the design of therapies for enhancing platelet reconstitution.

    • Alejandra Sanjuan-Pla
    • , Iain C. Macaulay
    •  & Sten Eirik W. Jacobsen

  • Letter |

    M-CSF, a myeloid cytokine released during infection and inflammation, instructs myeloid lineage fate in single haematopoietic stem cells by directly inducing PU.1, a known myeloid lineage master regulator; this shows that specific cytokines can act directly on haematopoietic stem cells to instruct a change of cell identity.

    • Noushine Mossadegh-Keller
    • , Sandrine Sarrazin
    •  & Michael H. Sieweke

  • Letter |

    In vivo ‘cellular barcoding’ shows that early haematopoietic progenitors are heterogeneous in the cell types that they produce, and this is partly due to an ‘imprinting’ of fate in progenitors, including for a separate dendritic cell lineage.

    • Shalin H. Naik
    • , Leïla Perié
    •  & Ton N. Schumacher

  • Letter |

    Endogenous prostaglandin E2 (PGE2) is a potent regulator of haematopoietic stem cell (HSC) retention in the bone marrow; inhibition of endogenous PGE2 signalling by non-steroidal anti-inflammatory drugs results in enhanced HSC and haematopoietic progenitor cell mobility via E-prostanoid 4 (EP4) receptor antagonism.

    • Jonathan Hoggatt
    • , Khalid S. Mohammad
    •  & Louis M. Pelus

  • Article |

    Autophagy is shown to be an essential mechanism that protects haematopoietic stem cells from metabolic stress; the transcription factor FOXO3A maintains a pro-autophagy gene expression program that poises haematopoietic stem cells to rapidly mount a protective autophagic response upon metabolic stress.

    • Matthew R. Warr
    • , Mikhail Binnewies
    •  & Emmanuelle Passegué

  • Letter |

    Immunoglobulin genes are expressed from either the maternal or paternal chromosome; it is now shown that in early haematopoietic stem cells, an individual cell can choose either of the two alleles, but as they develop they become committed to only one.

    • Marganit Farago
    • , Chaggai Rosenbluh
    •  & Yehudit Bergman

  • News & Views |

    Different cell types produce signals that regulate the activity of blood-forming stem cells. A study shows that certain rare mesenchymal cells surrounding blood vessels are the main source of one such signal in mice. See Article p.457

    • Ilya A. Shestopalov
    •  & Leonard I. Zon

  • 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

  • Books & Arts |

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

    • Caleb Finch

  • 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

  • Letter |

    One of two papers showing the generation of haematopoietic stem cells (HSCs) from the ventral wall of the dorsal aorta in live zebrafish embryos. Here, using imaging of live zebrafish, HSCs are shown to emerge directly from the aorta floor. This process does not involve cell division but movement of single endothelial cells out of the aorta ventral wall into the sub aortic space, where they transform into haematopoietic cells.

    • Karima Kissa
    •  & Philippe Herbomel

  • Letter |

    One of two papers showing the generation of haematopoietic stem cells (HSCs) from the ventral wall of the dorsal aorta in live zebrafish embryos. Here, combined fluorescent reporter transgenes, confocal time-lapse microscopy and flow cytometry identify and isolate the stepwise intermediates as aortic haemogenic endothelium transitions to nascent HSCs. HSCs generated from this haemogenic endothelium are the lineal founders of virtually all of the adult haematopoietic system.

    • Julien Y. Bertrand
    • , Neil C. Chi
    •  & David Traver

  • Letter |

    De novo emergence of phenotypically defined haematopoietic stem cells (Sca1+, c kit+, CD41+) directly from ventral aortic haemogenic endothelial cells is shown in mice. Although the study did not visualize live embryos, it instead developed a dissection procedure to visualize the deeply located aorta.

    • Jean-Charles Boisset
    • , Wiggert van Cappellen
    •  & Catherine Robin

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