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  • Cellular senescence induced by DNA replication and telomere attrition contributes to organ dysfunction, inflammation and impaired immunity. A study reveals that antigen-presenting cells provide telomeric DNA to CD4+ T cells in synaptic contact, which enables the suspension of senescence, T cell expansion and long-lived immunity.

    • Anna Carey
    • Laura Niedernhofer
    • Christina Camell
    News & Views
  • The Rag GTPases form the link between extracellular nutrients and the activation of mTORC1. RagA/B and RagC/D have been considered functionally redundant, but two studies now show that each isoform and gene have specific features, making their control of mTORC1 activity more nuanced and complex than previously appreciated.

    • Nicola Alesi
    • Elizabeth P. Henske
    News & Views
  • Aggregation of the RNA-binding protein TDP-43 is commonly observed in neurodegenerative disorders. A new study reveals that this process may be blocked by HSPB1, a small heat shock protein that can also regulate TDP-43 phase separation. This may be relevant to neurodegeneration, as loss of HSPB1 correlates with TDP-43 pathology.

    • Yuna M. Ayala
    • Zachary R. Grese
    News & Views
  • The mechanisms that underlie cell identity remain poorly understood. A study now dissects the transcriptional trajectories of single cells undergoing malignant transformation or reprogramming to pluripotency and reveals regulators of cell plasticity in these biological processes.

    • Bruno Di Stefano
    News & Views
  • NADPH levels serve as a biomarker of sensitivity to ferroptosis, but the regulators that detect cellular NADPH levels and modulate downstream ferroptosis responses are unknown. A study now identifies MARCHF6 in the ubiquitin system as an NADPH sensor that suppresses ferroptosis.

    • Chao Mao
    • Boyi Gan
    News & Views
  • Aberrant subcellular localization of proteins contributes to the pathogenesis of cancer. A study now reports that the mis-localization of METTL3, a nuclear N6-adenosine methyltransferase, to the cytoplasm promotes gastric cancer by enhancing mRNA translation of a subset of oncogenes, independently of the N6-methyladenosine (m6A) modification.

    • Sylvain Delaunay
    • Michaela Frye
    News & Views
  • EGFR is an oncogene that is frequently amplified in glioblastoma. A new study suggests a tumour-suppressive role of EGFR in EGFR-amplified glioblastoma regulated by ligand abundance. Increased EGFR ligand in EGFR-amplified glioblastoma suppresses invasion by upregulating BIN3 and inhibiting activation of Rho GTPases.

    • Mary Clare Beytagh
    • William A. Weiss
    News & Views
  • Primary cilia transduce cues, including Hedgehog (Hh) signals, and possess doublet microtubules that interact with kinesin motors. The kinesin KIF7 is important for Hh signalling and binds to GLI transcription factors. Haque et al. reveal that, surprisingly, GLI proteins bind a DNA-like part of KIF7 to promote their accumulation at the ciliary tip.

    • Dhivya Kumar
    • Jeremy F. Reiter
    News & Views
  • Intrinsically disordered regions are a ubiquitous class of protein domains that lack a fixed 3D structure. Here, an evolutionarily conserved family of disordered CO2 sensors has been discovered, expanding the growing repertoire of disordered regions that respond to changes in the cellular environment.

    • Ryan J. Emenecker
    • Alex S. Holehouse
    News & Views
  • In Caenorhabditis elegans, RNAi-initiated gene silencing can persist for multiple generations. A study shows that this heritable silencing requires parallel contributions of both a nuclear transcriptional silencing pathway and perinuclear condensate-localized poly(UG)-tailed transcripts to produce abundant germline siRNAs in adult progeny.

    • Nicole M. Bush
    • Craig P. Hunter
    News & Views
  • Multiple methods for deriving human cortical organoids have been established in the past decade. A study now systematically compares patterning strategies and shows that combined WNT and dual SMAD inhibition is superior to dual SMAD inhibition alone in inducing robust cortical identity in 3D human pluripotent stem-cell aggregates.

    • Alexander Atamian
    • Marcella Birtele
    • Giorgia Quadrato
    News & Views
  • Human naive pluripotent stem cells are generally believed to possess an unrestricted capacity to differentiate into both embryonic and extraembryonic lineages. However, two new studies now uncover a role for the Polycomb repressive complex 2 (PRC2) as a lineage gatekeeper that shields the potency of these cells.

    • Sergi Aranda
    • Livia Condemi
    • Luciano Di Croce
    News & Views
  • The lysosome is an essential organelle that degrades extra- and intra-cellular components and acts as a signaling hub. A study in Caenorhabditis elegans now shows that the lysosome mediates inter-tissue communication from periphery to neurons to regulate lifespan via fatty acid breakdown and secretion.

    • Jason Wayne Miklas
    • Anne Brunet
    News & Views
  • The nuclear pore complex (NPC) regulates transport of macromolecules into and out of the nucleus. A study now shows that mechanical force applied on the nucleus affects the transport rates across the NPC diffusion barrier, modulating the nuclear localization of certain cargos.

    • Stefan Petrovic
    • André Hoelz
    News & Views
  • Fibroblasts become activated during wound repair and rapidly return to a ‘resting’ state, and are thus critical for normal tissue homeostasis and tumour development. A new study now reveals an important pro-tumorigenic role for the stress response in cancer-associated fibroblasts that may offer a new opportunity to limit tumour progression.

    • Douglas V. Faget
    • Sheila A. Stewart
    News & Views
  • Although cardiac cell therapy has been intensely studied, the high expectations are still an unmet goal. A study now characterizes the translational potential and mode of action of human ventricular progenitors (HVPs) derived from embryonic stem cells, as a source for cardiac cell therapy.

    • Louk Theodoor Timmer
    • Eva van Rooij
    News & Views
  • Cytosolic DNA sensing by the cGAS–STING pathway is critical for sustaining an innate immune defense program. A new study shows that the cGAS–STING pathway signals by a non-canonical mechanism to control protein translation through the unfolded protein response sensor PERK, and thereby contributes to cellular senescence and organ fibrosis.

    • Younis Hazari
    • Claudio Hetz
    News & Views
  • Phosphoinositide signalling regulates cellular processes and is hijacked by pathogens. Classically, phosphoinositides are produced by kinase- and phosphatase-catalysed reactions. A study now reveals an unprecedented, kinase- and ATP-free synthesis of PtdIns(3,4)P2 via a phosphotransferase mechanism during bacterial infection.

    • Xiaofu Cao
    • Jeremy M. Baskin
    News & Views
  • Organic acidurias are inherited disorders that can severely affect mitochondria. A study in Caenorhabditis elegans suggests that binding of a toxic metabolite to a factor crucial for mitochondrial structure may contribute to disease mechanisms.

    • Till Klecker
    • Benedikt Westermann
    News & Views
  • Overload of proteasomal clearance triggers formation of a large protein inclusion called the aggresome, which shares similarities with protein aggregates seen in neurodegenerative diseases such as Huntington’s. A new study uncovers how centrosome and centriolar satellite components facilitate stepwise assembly of aggresomes.

    • Elisa Vitiello
    • Fanni Gergely
    News & Views