Haematopoietic stem cells

  • Article |

    An analysis of skeletal stem cells in mice reveals that bone ageing occurs at the level of local niches affecting skeletal and haematopoietic lineage output, which may influence systemic aspects of multi-organ physiological ageing.

    • Thomas H. Ambrosi
    • , Owen Marecic
    •  & Charles K. F. Chan
  • Article |

    Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

    • Alexander G. Bick
    • , Joshua S. Weinstock
    •  & Pradeep Natarajan
  • Article |

    Single-molecule fluorescence in situ hybridization and live-cell imaging are used to study the contribution of transcriptional noise to stem cell heterogeneity, revealing that stochastic transcription dynamics are conducive to concomitant stem-cell maintenance and tissue homeostasis.

    • Justin C. Wheat
    • , Yehonatan Sella
    •  & Ulrich Steidl
  • Article |

    MLLT3 is identified as a crucial regulator of the self-renewal of human haematopoietic stem cells, and helps to maintain an active chromatin state in haematopoietic stem-cell regulatory genes during culture.

    • Vincenzo Calvanese
    • , Andrew T. Nguyen
    •  & Hanna K. A. Mikkola
  • Article |

    The transcriptional landscape of cell populations of the mouse bone marrow microenvironment, mapped at single-cell resolution, reveals cellular heterogeneity in this niche as well as substantial transcriptional remodelling under stress conditions.

    • Anastasia N. Tikhonova
    • , Igor Dolgalev
    •  & Iannis Aifantis
  • Letter |

    In zebrafish embryogenesis, nascent haematopoietic stem and progenitor cells (HSPCs), homing to a vascular niche for retention, are ushered by patrolling and guiding macrophages through integrin-mediated cell-cell recognition.

    • Dantong Li
    • , Wenzhi Xue
    •  & Weijun Pan
  • Letter |

    Transposon tagging to clonally trace progenitors and stem cells provides evidence for a substantially revised roadmap for unperturbed haematopoiesis, and highlights unique properties of multipotent progenitors and haematopoietic stem cells in situ.

    • Alejo E. Rodriguez-Fraticelli
    • , Samuel L. Wolock
    •  & Fernando D. Camargo
  • Article |

    During emergency myelopoiesis in mice, clusters of self-renewing granulocyte/macrophage progenitors (GMP) are transiently formed in the bone marrow cavity to produce a burst of myeloid cells; in leukaemia, GMP clusters persist and constantly generate myeloid leukaemia cells.

    • Aurélie Hérault
    • , Mikhail Binnewies
    •  & Emmanuelle Passegué
  • Article |

    These preclinical studies outline a CRISPR-based methodology for correcting β-globin gene mutations in haematopoietic stem cells to advance the development of next-generation therapies for β-haemoglobinopathies.

    • Daniel P. Dever
    • , Rasmus O. Bak
    •  & Matthew H. Porteus
  • Article |

    Bone marrow endothelial cells have dual roles in the regulation of haematopoietic stem cell maintenance and in the trafficking of blood cells between the bone marrow and the blood circulatory system; this study shows that these different functions are regulated by distinct types of endothelial blood vessels with different permeability properties, affecting the metabolic state of their neighbouring stem cells.

    • Tomer Itkin
    • , Shiri Gur-Cohen
    •  & Tsvee Lapidot
  • Letter |

    Until recently, complex multi-parameters were required for the isolation and identification of haematopoietic stem cells, complicating study of their biology in situ; here the authors have found that expression of a single gene, Hoxb5, defines haematopoietic stem cells with long-term reconstitution capacity, and that these cells are mainly found in direct contact with endothelial cells.

    • James Y. Chen
    • , Masanori Miyanishi
    •  & Irving L. Weissman
  • Letter |

    The role of mitochondria in haematopoietic stem-cell maintenance has not been examined in detail; here mitofusin 2, which modulates mitochondrial fusion and tethering of endoplasmic reticulum to the mitochondria, is shown to be necessary for the maintenance of haematopoietic stem cells with extensive lymphoid potential.

    • Larry L. Luchsinger
    • , Mariana Justino de Almeida
    •  & Hans-Willem Snoeck
  • Article |

    Haematopoietic stem cells normally reside in a bone marrow niche but they are recruited to the spleen after physiological stresses; here, endothelial cells and stromal cells around sinusoidal blood vessels of the spleen are shown to secrete key niche factors to support this process.

    • Christopher N. Inra
    • , Bo O. Zhou
    •  & Sean J. Morrison
  • Letter |

    An in vivo imaging-based competitive transplant screen in zebrafish identifies epoxyeicosatrienoic acids as enhancers of haematopoietic stem and progenitor cell (HSPC) engraftment; these derivatives of arachidonic acid also promote zebrafish developmental HSPC specification through a PI(3)K-dependent AP-1 and runx1 transcriptional program and their pro-engraftment effect is conserved in mammals (indicating clinical potential).

    • Pulin Li
    • , Jamie L. Lahvic
    •  & Leonard I. Zon
  • Letter |

    Here, DNA damage is shown to occur as a direct consequence of inducing haematopoietic stem cells to exit quiescence in response to conditions of stress; in mice with mutations modelling those seen in Fanconi anaemia, this leads to a complete collapse of the haematopoietic system.

    • Dagmar Walter
    • , Amelie Lier
    •  & Michael D. Milsom
  • Letter |

    Inducible genetic labelling of haematopoietic stem cells (HSCs) and linked mathematical modelling show that at least 30% of all HSCs are productive, and that adult haematopoiesis is largely sustained by ‘short-term’ downstream stem cells that operate near self-renewal in the steady state; HSC fate mapping provides a quantitative model for better understanding of HSC functions in health and disease.

    • Katrin Busch
    • , Kay Klapproth
    •  & Hans-Reimer Rodewald
  • 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