Browse Articles

  • Article |

    Boyd et al. monitored the effects of patient-derived acute myeloid leukaemia (AML) cells on human HSPCs in vivo and found that AML impairs bone marrow adipocyte differentiation, and this in turn impedes healthy endogenous haematopoiesis.

    • Allison L. Boyd
    • , Jennifer C. Reid
    • , Kyle R. Salci
    • , Lili Aslostovar
    • , Yannick D. Benoit
    • , Zoya Shapovalova
    • , Mio Nakanishi
    • , Deanna P. Porras
    • , Mohammed Almakadi
    • , Clinton J. V. Campbell
    • , Michael F. Jackson
    • , Catherine A. Ross
    • , Ronan Foley
    • , Brian Leber
    • , David S. Allan
    • , Mitchell Sabloff
    • , Anargyros Xenocostas
    • , Tony J. Collins
    •  & Mickie Bhatia
  • Letter |

    Rondinelli et al. show that EZH2-mediated H3K27me3 at stalled replication forks recruits MUS81 nuclease to facilitate fork degradation. Loss of EZH2 contributes to PARPi resistance in BRCA2-deficient tumours.

    • Beatrice Rondinelli
    • , Ewa Gogola
    • , Hatice Yücel
    • , Alexandra A. Duarte
    • , Marieke van de Ven
    • , Roxanne van der Sluijs
    • , Panagiotis A. Konstantinopoulos
    • , Jos Jonkers
    • , Raphaël Ceccaldi
    • , Sven Rottenberg
    •  & Alan D. D’Andrea
  • Article |

    Gilot et al. have found that TYRP1 mRNA, in addition to coding for TYRP1 protein, can promote melanoma by sequestering the tumour suppressor miR-16, thus de-repressing the mRNA transcription of miR-16 target RAB17, which is involved in melanoma cell proliferation.

    • David Gilot
    • , Mélodie Migault
    • , Laura Bachelot
    • , Fabrice Journé
    • , Aljosja Rogiers
    • , Emmanuelle Donnou-Fournet
    • , Ariane Mogha
    • , Nicolas Mouchet
    • , Marie-Laure Pinel-Marie
    • , Bernard Mari
    • , Tristan Montier
    • , Sébastien Corre
    • , Arthur Gautron
    • , Florian Rambow
    • , Petra El Hajj
    • , Rania Ben Jouira
    • , Sophie Tartare-Deckert
    • , Jean-Christophe Marine
    • , Brice Felden
    • , Ghanem Ghanem
    •  & Marie-Dominique Galibert
  • News and Views |

    Recycling from endosomes to the plasma membrane is an important step in cell homeostasis. The retromer/SNX27/WASH complex recycles numerous receptors, but key ones are still unaccounted for. Now a related conserved heterotrimer, called retriever, has been identified that, together with SNX17, the CCC complex and WASH, mediates the recycling of α5β1 integrins.

    • Catherine Rabouille
  • News and Views |

    It is generally accepted that protein function depends on a defined 3D structure, with unfolding and aggregation dealing a final blow to functionality. A study now shows that the regulated exposure of an unstructured region in yeast pyruvate kinase triggers reversible aggregation to preserve protein function under stress.

    • Jörg Höhfeld
  • News and Views |

    During muscle development, nuclei travel from the centre of the myofibre to the periphery, a process defective in certain diseases. A new study reveals that this movement is due to centripetal forces imposed on nuclei by the crosslinking and contraction of myofibrils.

    • Jonathan N. Rosen
    •  & Mary K. Baylies
  • News and Views |

    Cancer cells preferentially metastasize to certain organs. A study in mouse models of breast cancer shows that the DKK1 negative regulator of WNT signalling inhibits tropism to the lung, but enhances tropism to the bone due to the differential regulation of canonical and non-canonical WNT signalling in the two microenvironments.

    • Wei Zheng
    •  & Jeffrey W. Pollard
  • News and Views |

    The cytokine tumour necrosis factor (TNF) and the toll-like receptors (TLRs) coordinate immune responses by activating inflammatory transcriptional programs, but these signals can also trigger cell death. Recent studies identify the MAP kinase substrate MK2 as a key player in determining whether cells live or die in response to TNF and TLR signalling.

    • Andrew Oberst
  • Article |

    Wu et al. show that prosurvival BCL-2 proteins disrupt SUFU repression of GLI activity, leading to GLI target gene expression. BH3 mimetics disable GLI transcriptional activity driven by HH pathway mutations.

    • Xiaofeng Wu
    • , Li-shu Zhang
    • , Jason Toombs
    • , Yi-Chun Kuo
    • , John Tyler Piazza
    • , Rubina Tuladhar
    • , Quinn Barrett
    • , Chih-wei Fan
    • , Xuewu Zhang
    • , Loren D. Walensky
    • , Marcel Kool
    • , Steven Y. Cheng
    • , Rolf Brekken
    • , Joseph T. Opferman
    • , Douglas R. Green
    • , Tudor Moldoveanu
    •  & Lawrence Lum
  • Article |

    Anderson et al. show that LIF, ActA and Wnt support self-renewal in both pluripotent and endodermal cells. Upon removal of insulin, they induce differentiation of naive PSCs into extra-embryonic primitive endoderm and primed PSCs into definitive endoderm.

    • Kathryn G. V. Anderson
    • , William B. Hamilton
    • , Fabian V. Roske
    • , Ajuna Azad
    • , Teresa E. Knudsen
    • , Maurice A. Canham
    • , Lesley M. Forrester
    •  & Joshua M. Brickman
  • Article |

    Dondelinger et al. and Menon et al. show that MAPKAP kinase-2 (MK2) phosphorylates RIPK1 to regulate TNF-mediated cell death as well as RIPK1 signalling in inflammation and bacterial infection.

    • Yves Dondelinger
    • , Tom Delanghe
    • , Diego Rojas-Rivera
    • , Dario Priem
    • , Tinneke Delvaeye
    • , Inge Bruggeman
    • , Franky Van Herreweghe
    • , Peter Vandenabeele
    •  & Mathieu J. M. Bertrand
  • Article |

    Dondelinger et al. and Menon et al. show that MAPKAP kinase-2 (MK2) phosphorylates RIPK1 to regulate TNF-mediated cell death as well as RIPK1 signalling in inflammation and bacterial infection.

    • Manoj B. Menon
    • , Julia Gropengießer
    • , Jessica Fischer
    • , Lena Novikova
    • , Anne Deuretzbacher
    • , Juri Lafera
    • , Hanna Schimmeck
    • , Nicole Czymmeck
    • , Natalia Ronkina
    • , Alexey Kotlyarov
    • , Martin Aepfelbacher
    • , Matthias Gaestel
    •  & Klaus Ruckdeschel
  • Article |

    Ganuza et al. track newly specified blood progenitors in the dorsal aorta of the mouse embryo and demonstrate that they are polyclonal in origin and that hundreds of mesodermal, endothelial and blood precursors establish lifelong haematopoiesis.

    • Miguel Ganuza
    • , Trent Hall
    • , David Finkelstein
    • , Ashley Chabot
    • , Guolian Kang
    •  & Shannon McKinney-Freeman
  • Article |

    Wu et al. find that tumour hypoxic conditions increase miR25/93 levels, which via targeting Ncoa3 downregulate the expression of the innate immune regulator cGAS, thus allowing escape of the anti-tumour immune response.

    • Min-Zu Wu
    • , Wei-Chung Cheng
    • , Su-Feng Chen
    • , Shin Nieh
    • , Carolyn O’Connor
    • , Chia-Lin Liu
    • , Wen-Wei Tsai
    • , Cheng-Jang Wu
    • , Lorena Martin
    • , Yaoh-Shiang Lin
    • , Kou-Juey Wu
    • , Li-Fan Lu
    •  & Juan Carlos Izpisua Belmonte
  • Article |

    McNally et al. identify the retriever complex as required for endosomal cargo recycling. Retriever binds SNX17, the CCC and WASH complexes to govern cell surface expression of integrins, receptors and transporters.

    • Kerrie E. McNally
    • , Rebecca Faulkner
    • , Florian Steinberg
    • , Matthew Gallon
    • , Rajesh Ghai
    • , David Pim
    • , Paul Langton
    • , Neil Pearson
    • , Chris M. Danson
    • , Heike Nägele
    • , Lindsey L. Morris
    • , Amika Singla
    • , Brittany L. Overlee
    • , Kate J. Heesom
    • , Richard Sessions
    • , Lawrence Banks
    • , Brett M. Collins
    • , Imre Berger
    • , Daniel D. Billadeau
    • , Ezra Burstein
    •  & Peter J. Cullen
  • Article |

    Lee et al. found that the ubiquitin-editing enzyme A20 promotes TGF-β1-induced EMT and metastases of breast cancer cells via ubiquitylation-mediated nuclear stabilization of Snail1.

    • Ji-Hyung Lee
    • , Su Myung Jung
    • , Kyung-Min Yang
    • , Eunjin Bae
    • , Sung Gwe Ahn
    • , Jin Seok Park
    • , Dongyeob Seo
    • , Minbeom Kim
    • , Jihoon Ha
    • , Jaewon Lee
    • , Jun-Hyeong Kim
    • , Jun Hwan Kim
    • , Akira Ooshima
    • , Jinah Park
    • , Donghyuk Shin
    • , Youn Sook Lee
    • , Sangho Lee
    • , Geert van Loo
    • , Joon Jeong
    • , Seong-Jin Kim
    •  & Seok Hee Park
  • News and Views |

    Three-dimensional brain organoid models have come into the spotlight as in vitro tools to recapitulate complex features of the brain. Four recent papers now leverage current technologies to generate new flavours of brain organoids and address aspects of brain biology which, to date, have been challenging to explore.

    • Lin Yang
    •  & Huck-Hui Ng
  • News and Views |

    Cellular senescence, a cell-autonomous growth arrest program, also executes pleiotropic non-cell-autonomous activities through the senescence-associated secretory phenotype (SASP). The innate cGAS–STING DNA-sensing pathway is now shown to regulate senescence by recognizing cytosolic DNA and inducing SASP factors, uncovering an unexpected link between these two previously unrelated pathways.

    • Marina Ruiz de Galarreta
    •  & Amaia Lujambio
  • News and Views |

    Brown adipose tissue is a key metabolic organ that oxidizes fatty acids and glucose to generate heat. Through epigenomic analyses of multiple adipose depots, the transcription factor nuclear factor I-A (NFIA) is now shown to drive the brown fat genetic program through binding to lineage-specific cis-regulatory elements.

    • Suzanne N. Shapira
    •  & Patrick Seale
  • News and Views |

    Induced pluripotent stem cells derived from aged donors (A-iPSCs) usually show genomic instability that affects their utility and raises concerns about their safety. Now, a study highlights the importance of ZSCAN10-dependent recovery of glutathione–ROS homeostasis in counteracting the genomic defects in A-iPSCs.

    • Clea Bárcena
    •  & Carlos López-Otín
  • News and Views |

    Cancer treatments often focus on killing tumour cells through apoptosis, which is thought to typically require mitochondrial outer membrane permeabilization (MOMP) and subsequent caspase activation. A study now shows that MOMP can trigger TNF-dependent, but caspase-independent cell death, suggesting a different approach to improve cancer therapy.

    • Brent E. Fitzwalter
    •  & Andrew Thorburn