News & Comment

  • News & Views |

    Post-translational histone modifications are important regulators of nuclear reprogramming. A study now reveals that histone lysine demethylase KDM4A-mediated H3K9me3 demethylation in mammalian oocytes is essential for zygotic genome activation and preimplantation development.

    • Julie Brind’Amour
    •  & Matthew C. Lorincz
  • News & Views |

    YAP and TAZ, paralogous mammalian genes, act as the key transcriptional effectors of the Hippo pathway. Two recent reports show that both YAP and TAZ form liquid–liquid phase-separated bodies that promote gene transcription by engaging in super-enhancers.

    • J. Matthew Franklin
    •  & Kun-Liang Guan
  • News & Views |

    Piwi proteins are aberrantly induced in human tumours, but their function in cancer has been poorly understood. A study now shows that in the absence of piRNA loading, human PIWIL1 promotes pancreatic cancer metastasis by acting as a co-activator of the anaphase-promoting complex/cyclosome (APC/C) to degrade the cell-adhesion protein Pinin.

    • Fan Yao
    •  & Li Ma
  • News & Views |

    The lack of endogenous reporter lines is a bottleneck in the study of subcellular dynamics in human adult stem cell (ASC)-derived organoids. An approach using CRISPR–Cas9-mediated homology-independent organoid transgenesis (CRISPR–HOT) in ASC-derived organoids now narrows the gap between basic research and translational studies in human organoids.

    • Qiutan Yang
    • , Koen C. Oost
    •  & Prisca Liberali
  • News & Views |

    Misfolded proteins in the endoplasmic reticulum (ER) are returned to the cytosol and destroyed by a process known as ER-associated degradation (ERAD). Hrd1 has been implicated as the channel that mediates the transport of ERAD substrates to the cytosol. A study demonstrates that Hrd1 is gated by autoubiquitination and a soluble ERAD substrate.

    • Miguel Betegon
    •  & Jeffrey L. Brodsky
  • News & Views |

    Gene editing holds promise for the treatment of cancers that are driven by well-characterised molecular alterations. A study now provides a proof of concept for the feasibility of in vivo gene editing to correct TERT mutations in glioblastoma, providing a platform for the direct manipulation of genetic alterations to reduce tumour growth.

    • Katie Troike
    •  & Justin D. Lathia
  • News & Views |

    Understanding the metabolic rewiring of pancreatic ductal adenocarcinoma is an emerging strategy for identifying cancer-associated liabilities and improving treatment. A new study now elucidates the function of the transaminase BCAT2 in the early stages of tumor development, providing insights that could stimulate novel therapeutic strategies.

    • Mattia Falcone
    •  & Oliver D. K. Maddocks
  • News & Views |

    The ribosome decodes messenger RNAs and constructs proteins based on the genetic blueprint. Ribosomes also associate with non-coding RNAs, such as PIWI-interacting RNA (piRNA) precursors, during the meiotic pachytene stage. Intriguingly, the ribosome mediates pachytene piRNA biogenesis by guiding endonucleolytic cleavage of piRNA precursors.

    • Yuanhui Mao
    •  & Shu-Bing Qian
  • News & Views |

    A mechanism of secretory autophagy explains aspects of the packaging of proteins and RNA into extracellular vesicles and paves the way to a better understanding of their biological roles and medical applications.

    • Janusz Rak
  • News & Views |

    The molecular clock regulates the rhythmic transcription of myriad genes, leading to a circadian pattern of expression of the encoded proteins. A study demonstrates circadian regulation of expression of components of the protein secretory pathway, providing a mechanism to generate circadian patterns of secreted protein expression.

    • Thomas P. Burris
  • News & Views |

    Different types of stromal cells in the bone marrow associate to form niches that support differentiating blood cells and ensure lifelong production of all major blood lineages. A study now combines single-cell and spatial transcriptomics with imaging to infer the cellular composition and spatial architecture of specific niches.

    • Daniel Lucas
    • , Nathan Salomonis
    •  & H. Leighton Grimes
  • News & Views |

    Tangential expansion of neural stem cells in the mammalian neocortex increases the number of cortical columns. A new study shows that neural stem cells that become detached from the apical surface during division regenerate an apical endfoot to ensure tangential expansion in the early stage but later lose this ability when radial expansion occurs.

    • Masafumi Tsuboi
    •  & Yukiko Gotoh
  • Editorial |

    Advances in CRISPR-based systems have greatly expanded the molecular toolbox for biologists. In this issue, we present the first of a Series of commissioned Review articles that highlight the progress made using CRISPR–Cas9 technology and its relevance for cell biological research.

  • News & Views |

    Tendons have limited regenerative potential, and injuries often cause scarring. A study now identifies a tendon stem cell population that contributes to regeneration and a tendon fibro–adipogenic progenitor population involved in fibrosis.

    • Ashley L. Titan
    •  & Michael T. Longaker
  • News & Views |

    In mammals, a circadian timing system composed of a master clock in the brain’s suprachiasmatic nucleus and oscillators in peripheral organs drives daily rhythms of behavior and physiology. A study now reveals that the periodic oxidation of the CLOCK protein enhances the amplitude of cyclic gene expression and affects the daily rhythms of behavior.

    • Ueli Schibler
  • News & Views |

    PTEN is a phosphatase that functions as a tumour suppressor by antagonizing the PI3K–AKT pathway. However, a study now demonstrates that translational variants of PTEN enable new interactions between PTEN and the COMPASS complex, identifying a new role for PTEN in modifying gene expression via COMPASS-mediated histone H3 lysine 4 methylation.

    • Justin Taylor
    •  & Omar Abdel-Wahab
  • News & Views |

    Pancreatic ductal adenocarcinoma displays high levels of cellular heterogeneity, which is associated with drug resistance and high metastatic rates. A new study shows that tetraspanin CD9 marks PDAC tumour-initiating cells and functions as a regulator of glutamine metabolism.

    • Xiphias Ge Zhu
    •  & Kivanc Birsoy
  • News & Views |

    After mitosis chromosomes are drastically reshaped. A study now charts the dynamics of this conformational change at high temporal resolution. During the shift from one loop-forming complex (condensin) to another (cohesin), an intermediate chromosome folding state exists in which neither of these complexes are associated with chromatin.

    • Ning Qing Liu
    •  & Elzo de Wit
  • News & Views |

    The non-specific lethal (NSL) complex is a highly conserved MOF acetyltransferase-containing complex. A recent study now shows that the NSL complex acetylates a new non-histone target, Lamin A/C and reveals the NSL complex as a crucial factor in maintaining nuclear architecture and genome integrity.

    • Varvara V. Popova
    •  & Jerry L. Workman
  • News & Views |

    Endosomes are central stations for converging proteins from biosynthetic pathways and endocytic routes. Many endosomal proteins are sorted to the plasma membrane or the Golgi despite the lysosome being the primary endosomal fate. SNX5 and SNX6 are now revealed to decode a conserved bipartite signal to mediate protein sorting to the Golgi or the plasma membrane.

    • Wanjin Hong
  • News & Views |

    Cell identity is shaped by a complex interplay between transcription factors, enhancers and genome organisation. A study now reveals a dynamic role for the transcription factor KLF4 in directing gene regulatory interactions during pluripotent cell reprogramming, demonstrating that transcription factors can function as chromatin organisers.

    • Peter J. Rugg-Gunn
  • News & Views |

    Assembly of the mitotic spindle requires timely separation of the centrosomes. Their movement apart is driven by the plus-end-directed kinesin Eg5. A new study demonstrates that the kinesin KIFC3 provides an opposing microtubule-based cohesive force that modulates centrosome separation and ensures accurate chromosome segregation.

    • Ciaran G. Morrison
  • News & Views |

    Tumours elicit an immune attack that can stifle their growth, but they can also recruit inflammatory immune cells that suppress this response. A new study identifies distinct immune subtypes of triple-negative breast cancer with two different inflammatory cell types: macrophages or neutrophils. The immune subtype dictates the response to immunotherapy.

    • Laura Maiorino
    •  & Mikala Egeblad
  • Obituary |

    Our mentor, Suzanne Eaton, tragically fell victim to homicide on 2 July 2019. The circumstances of her disappearance and death have shocked scientists and the public alike, worldwide. From the moment she went missing, the members of her family, laboratory and colleagues have received admirable and touching support from the scientific community. This outpouring stands testament to the inspiration that Suzanne—a world-leader scientist, creative pioneer and beloved mentor—is to all of us.

    • Valentina Greco
    •  & Suhrid Ghosh
  • News & Views |

    Migrasomes are a recently discovered type of extracellular vesicles that are characteristically generated along retraction fibers in migrating cells. Two studies now show how migrasomes are formed and how they function in the physiologically relevant context of the developing zebrafish embryo.

    • Stefania Tavano
    •  & Carl-Philipp Heisenberg
  • News & Views |

    Activation of the receptor EGFR (ERBB1) occurs in response to viral infections and regulates antiviral immunity. A new study now shows that the receptor HER2 (ERBB2) negatively regulates STING signaling in response to DNA viruses and expands the model and mechanisms by which surface-receptor tyrosine kinases perform important intracellular regulatory functions.

    • Ian D. Odell
    •  & Richard A. Flavell
  • News & Views |

    Loss-of-function mutations in the ubiquitin ligase Parkin are a cause of Parkinson’s disease. Parkin also has tumour-suppressor activity, although how Parkin prevents cancer is unclear. Unexpectedly, Parkin is found to suppress cancer by inhibiting an inflammatory type of cell death called necroptosis.

    • Kai Cao
    •  & Stephen W. G. Tait
  • News & Views |

    Tissue renewal requires proliferative progenitors with long-lasting potential. Designated stem cells within specialized niches are considered to be the primary mechanism for this requirement. Recent studies show that dispersed equipotent progenitors are sufficient to account for fast-paced cellular dynamics in skin oil glands and foetal gut epithelium.

    • Qing Nie
    •  & Maksim V. Plikus
  • News & Views |

    Different subclones cooperate to support tumour heterogeneity and growth, but the effect on metastasis is unclear. A new study now shows that, as non-cell-autonomous drivers, minor cancer cell subclones instigate growth at distant sites of otherwise non-metastatic cancer cells. This is mediated systemically by perturbation in the metastatic tissue.

    • Luigi Ombrato
    •  & Ilaria Malanchi
  • News & Views |

    The ability of cancer cells to adapt to external and internal stresses is critical for tumourigenesis. A new study now shows that the integrated stress response is critical for tumour cell adaptation to stress induced by c-MYC activation, providing mechanistic insights into tumour responses to intrinsic stresses with implications for cancer therapies.

    • Kirk A. Staschke
    •  & Ronald C. Wek
  • News & Views |

    Tumour-secreted microvesicles carry bioactive molecules that can be transferred to recipient cells, impacting tumour progression. A study now shows that ARF6 drives miRNA loading into tumour microvesicles through interaction with pre-miRNA–Exportin-5 complexes, thus shedding light on specific cargo packaging mechanisms.

    • Gonçalo Rodrigues
    • , Haiying Zhang
    •  & David Lyden
  • News & Views |

    Centromere identity must be maintained through multiple generations. A new study reveals a Constitutive Centromere-Associated Network (CCAN)-dependent retention of CENP-A, a key epigenetic mark for centromeres, in centromeres during DNA replication and a replication-dependent error correction to eliminate ectopic CENP-A in chromosome arms.

    • Masatoshi Hara
    •  & Tatsuo Fukagawa
  • News & Views |

    Embryonic stem cells derived from the inner cell mass can differentiate to all embryonic lineages of any adult cell type and to a limited extent to extra-embryonic tissues. A study now allows the generation of pig and human stem cells with enhanced differentiation potential towards all embryonic and extra-embryonic fates, one step closer to the totipotent state of the fertilized egg.

    • Fred Etoc
    •  & Ali Brivanlou
  • News & Views |

    IRE1α is an endoplasmic reticulum (ER) transmembrane protein known for a crucial role in regulating the unfolding protein response. A study now shows that IRE1α interacts with the main ER Ca2+ channel InsP3Rs and facilitates the transfer of Ca2+ from the ER into mitochondria, thus driving cellular metabolism.

    • Roland Malli
    •  & Wolfgang F. Graier
  • News & Views |

    Yap signalling is crucial for intestinal regeneration, but its role is largely dispensable in homeostasis. Two studies now reveal Yap-dependent mechanisms of intestinal regeneration and tissue organization: transient expansion of a rare cell type after damage in vivo and Notch–Dll activation for symmetry breaking in organoid development.

    • Vivian S. W. Li
  • Editorial |

    RNA molecules are more than messengers between DNA and protein and exhibit rich regulatory functions in development and disease. In this issue, we present a Focus on regulatory RNAs with specially commissioned Review articles that discuss recent advances in this fast-growing area.

  • News & Views |

    Rag GTPases play a crucial role in mTORC1 activation by promoting its recruitment to the lysosomal surface in a nutrient-dependent manner. A study now identifies a family of lysosomal G-protein-coupled receptors as modulators of Rag GTPases localization and activation, adding one more component to the fast-growing mTOR regulatory network.

    • Rosa Puertollano
  • News & Views |

    Haematopoietic stem cells (HSCs) are maintained in vivo by intrinsic programs and extrinsic niche signals. Ex vivo expansion of HSCs is limited, owing to reduced stem cell maintenance factors. A study now shows that rejuvenated niche cells can be obtained by transcriptional rewiring of specific genes that maintain and expand HSCs ex vivo.

    • Aparna Venkatraman
    •  & Linheng Li
  • News & Views |

    Components of the spliceosome are frequently mutated in haematopoietic malignancies. Identification of mis-spliced genes promoting transformation will uncover novel targeted therapies. Now, a long isoform of IRAK4 is shown to be upregulated in a subset of acute myeloid leukaemia patients, conferring susceptibility for IRAK4 inhibition therapy.

    • Maria Guillamot
    •  & Iannis Aifantis
  • News & Views |

    Osteoclasts are known for their role in bone resorption. A study now shows that a vascular–associated osteoclast subtype at the growth plate also regulates blood vessel growth in bone and is supported by type H endothelial cells. These type H capillaries, in turn, release proteinases that promote cartilage degradation.

    • Jameel Iqbal
    •  & Mone Zaidi
  • News & Views |

    MicroRNAs (miRNAs) repress target mRNAs, often with exquisite tissue specificity. Wang et al. exploit the specific expression of miRNAs to regulate guide production for Cas9. Their method enables novel strategies to simultaneously measure the activity of multiple miRNAs and restrict Cas9 binding or genome editing to precisely defined cell types.

    • Karina Jouravleva
    •  & Phillip D. Zamore
  • News & Views |

    HIV particles incorporate host membrane proteins into their envelope to evade the immune system and infect other cells. A study now shows that Gag assembly on the host cell membrane produces a raft-like nanodomain favourable for protein partitioning due to a transbilayer coupling mechanism assisted by long saturated chain lipids and cholesterol.

    • Joanna Podkalicka
    •  & Patricia Bassereau
  • News & Views |

    Macrophages modulate mammary tumour response to chemotherapy. A new study shows that targeted elimination of macrophages elicits a type I interferon response in the tumour microenvironment that enhances the efficacy of platinum- but not taxane-based chemotherapy, underscoring complex regulatory roles for macrophages in chemotherapy-treated tumours.

    • Michele De Palma
    • , Sina Nassiri
    •  & Chiara Cianciaruso
  • News & Views |

    Epithelial–mesenchymal transition (EMT) is crucial for development, and for dissemination and invasion of cancer cells. A study now identifies the apical–basolateral polarity status of epithelia as a checkpoint for EMT induction and tumour metastasis through aPKC–Par3-regulated degradation of the EMT transcription factor SNAI1.

    • Oana-Diana Persa
    •  & Carien M. Niessen
  • News & Views |

    Healthy and malignant haematopoietic stem cells (HSCs) must overcome a variety of cell intrinsic and extrinsic stresses to maintain their functionality. Now, IRE1α –XBP1 signalling is shown to protect HSCs and to promote survival of, and confer competitive advantages to, NRAS-mutated pre-leukaemic cells.

    • Marina Scheller-Wendorff
    •  & Carsten Müller-Tidow
  • News & Views |

    Cell metabolism ensures that cell dynamics and continued renewal are supported by a constant flow of matter that consumes energy. A new study shows that cell metabolism is sensitive to mechanical cues, revealing that the level of cell contraction modulates the production and storage of lipids, which could serve as fuel for energy production.

    • Manuel Théry
    •  & Mario Pende
  • News & Views |

    Patients with diabetes could benefit from cell-based insulin therapy, but the supply of human islet tissue is limited. A study now reports an approach in which human-pluripotent-stem-cell-derived islet β-cells are purified and re-aggregated to generate cells that more closely resemble mature human β-cells.

    • Hans E. Hohmeier
    • , Jie An
    •  & Christopher B. Newgard
  • Editorial |

    Science thrives on the free exchange of ideas and collaboration between diverse groups, with researcher mobility greatly accelerating progress. With isolationist rhetoric increasingly dominating the political discourse in many countries, it is important to recognize the value of migration in science.

  • News & Views |

    AKT, also known as protein kinase B, is one of the most frequently dysregulated serine/threonine kinases in cancer, and its hyperactivity drives tumorigenesis and chemotherapy resistance. Two studies now find that AKT methylation by the methyltransferase SETDB1 is an early step in its oncogenic activation.

    • Amelia K. Luciano
    •  & David A. Guertin