Cell - a Cell Press journal

Cell - a Cell Press journal

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Cell aims to publish the most exciting and provocative research in biology. Posts by Scientific Editors on the Cell editorial team. See the latest papers at https://www.cell.com/cell/

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Cell - a Cell Press journal
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Now online! In vivo genome-editing therapy for Duchenne muscular dystrophy: Preclinical studies and first-in-human trial

dlvr.itIn vivo genome-editing therapy for Duchenne muscular dystrophy: Preclinical studies and first-in-human trialA single-dose AAV-CRISPR therapy restores dystrophin in humanized DMD mice and achieves durable editing with manageable safety in non-human primates. In a first-in-human DMD trial, the therapy yields molecular evidence of muscle editing but reveals a fatal dose-dependent immune complication, highlighting the urgent need to expand the safety margin of systemic AAV-CRISPR treatments.
Cell - a Cell Press journal
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Now online! Perforin triggers iron-induced mitochondrial damage to drive ferroptosis and anti-tumor immunity

dlvr.itPerforin triggers iron-induced mitochondrial damage to drive ferroptosis and anti-tumor immunityPerforin is best known for delivering granzymes into tumor cells, but this study shows it has a second, independent killing function: it drives iron uptake and mitochondrial iron overload that trigger ferroptosis. This granzyme-independent pathway links cytotoxic immunity to iron metabolism, predicts patient response to checkpoint blockade, and points to iron supplementation as a possible lever for boosting anti-tumor immunity.
Cell - a Cell Press journal
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Now online! MCT6 is an intestinal Lac-Phe exporter required for metformin-associated weight loss

dlvr.itMCT6 is an intestinal Lac-Phe exporter required for metformin-associated weight lossThe orphan transporter MCT6 is the route by which the meal- and exercise-associated metabolite Lac-Phe exits intestinal cells and enters the blood. Mice lacking gut MCT6 cannot maintain normal circulating Lac-Phe levels and exhibit resistance to metformin-associated weight loss, establishing metabolite export as a regulatory node for systemic action.
Cell - a Cell Press journal
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Now online! Lifestyle-induced regulatory T cell fragility primes adverse events after immune checkpoint blockade

dlvr.itLifestyle-induced regulatory T cell fragility primes adverse events after immune checkpoint blockadeDietary and microbial alterations increase susceptibility to irAEs by promoting IFN-Ξ³-driven Treg fragility and cytotoxic tissue-resident T cell responses. Treg-specific disruption of IFN-Ξ³ signaling restores tissue homeostasis and reduces irAEs without compromising antitumor immunity, highlighting Treg stability as a potential therapeutic strategy for limiting checkpoint blockade toxicity.
Cell - a Cell Press journal
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Now online! In vivo Gene Writing with engineered retrotransposons

dlvr.itIn vivo Gene Writing with engineered retrotransposonsComputational reconstruction, screening, and engineering of non-LTR retrotransposons uncovers elements, termed Gene Writers, that enable stable transgene integration in human cells using all-RNA delivery. After extensive characterization and optimization, Gene Writers is deployed to generate functional CAR-T cells in vivo in a humanized mouse model.
Cell - a Cell Press journal
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Now online! A bioavailable GPX4 inhibitor for ferroptosis induction in vivo and tumor suppression

dlvr.itA bioavailable GPX4 inhibitor for ferroptosis induction in vivo and tumor suppressionSelective pharmacological induction of ferroptosis in vivo has remained difficult. By developing the bioavailable GPX4 inhibitor KY0418, this work links systemic ferroptosis induction to tissue metabolic remodeling and demonstrates context-dependent suppression of tumor progression, including metastatic spread.
Cell - a Cell Press journal
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Now online! Contrasting demographic impacts of Roman colonization and early medieval migrations in the Iberian Peninsula

dlvr.itContrasting demographic impacts of Roman colonization and early medieval migrations in the Iberian PeninsulaRoman and post-Roman Iberia was transformed by extensive mobility across the Mediterranean, with large-scale inputs from Eastern Mediterranean and North African populations reshaping its genetic landscape. During the migration period, Central-Northern European ancestry arrived largely through elite-associated groups that intermarried with local populations but did not replace the highly diverse population that had formed under Roman rule.
Cell - a Cell Press journal
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Now online! Proteomic atlas of T cell exhaustion defines proteostatic collapse

dlvr.itProteomic atlas of T cell exhaustion defines proteostatic collapseA multi-omic atlas of human T cell exhaustion reveals that dysfunctional T cells undergo broad remodeling of protein turnover and ubiquitin regulation that is not captured by transcriptomic analysis. The E3 ubiquitin ligase RNF166 regulates T cell persistence and anti-tumor function, highlighting proteostasis as a targetable axis for improving immunotherapy.
Cell - a Cell Press journal
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Now online! The pyrin inflammasome senses OCTN2-mediated uptake of extracellular ʟ-carnitine from muscle injury or ingestion

dlvr.itThe pyrin inflammasome senses OCTN2-mediated uptake of extracellular ʟ-carnitine from muscle injury or ingestionʟ-Carnitine is a nonproteinogenic amino acid highly abundant in myocytes, and both excess ingestion of myocytes and myocyte necrosis are associated with systemic inflammation. Here, we find that the pyrin inflammasome senses extracellular ʟ-carnitine through the high-affinity carnitine transporter OCTN2 (SLC22A5) and this leads to IL-1β-mediated inflammation. Our findings position OCTN2 as a potential target to reduce inflammation from exogenous or endogenous sources of extracellular ʟ-carnitine.

Cell - a Cell Press journal reposted

Cell Press
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Curious about how an accepted paper is processed at Cell Press? Our Head of Production Andy Smith details steps our production team takes to support authors throughout the publication process. To watch the full video, visit: www.cell.com/video-do/beh...

Cell - a Cell Press journal
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Now online! Functional diversification of the cephalopod proteome by RNA editing

dlvr.itFunctional diversification of the cephalopod proteome by RNA editingColeoid cephalopods edit their RNA at a level far beyond other animals, but the functional consequences to the proteome have been largely unknown. Proteomic detection of recoded sites reveals that single amino acid edits alter protein stability, subcellular localization, post-translational modification, and organelle function.
Cell - a Cell Press journal
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Now online! An opioid efficacy switch for reversible optical control of analgesia

dlvr.itAn opioid efficacy switch for reversible optical control of analgesiaAzo-morphine-3 (AM-3) is a photoswitchable ligand that toggles between low and high efficacy states to control mu-opioid receptor activity in vitro and in vivo both in the brain and periphery. AM-3 provides a powerful tool to probe the structural basis of opioid efficacy and enables spatiotemporally precise control of analgesia across pain models with reduced side effects compared with systemic drugs.
Cell - a Cell Press journal
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Now online! Cellular self-organization orchestrates ferroptosis propagation

dlvr.itCellular self-organization orchestrates ferroptosis propagationLocal cell-cell interactions give rise to emergent cellular patterns that encode ferroptosis-sensitive and -resistant fates and establish polarized lipid organization within cells. These coupled biochemical and biophysical properties enable self-organized cell populations to orient and confine otherwise isotropic, unbounded ferroptosis propagation, revealing a systems-level mechanism that regulates collective cell fate.
Cell - a Cell Press journal
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Now online! Mitochondria-targeted tetraoxanes initiate lipid peroxidation to drive ferroptosis and tumor suppression

dlvr.itMitochondria-targeted tetraoxanes initiate lipid peroxidation to drive ferroptosis and tumor suppressionPan et al. report tetraoxane-containing compounds WMK-1/2 as first-generation mitochondrial lipid peroxidation inducers that bypass GPX4- and retinol-mediated defenses to trigger a distinct β€œmito-ferroptosis” sub-pathway, demonstrating potent bioavailable tumor-suppressive activity across multiple in vivo models.
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Cell - a Cell Press journal
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Now online! A phenome-wide structural variant map from 467,152 UK Biobank genomes

dlvr.itA phenome-wide structural variant map from 467,152 UK Biobank genomesBy studying nearly half a million human genomes, this work shows that structural variants, large changes in DNA sequence greater than 50 base pairs, are an important and previously underrecognized source of human disease risk. The resulting resource reveals rare and regulatory structural variants linked to disease, providing insights into human biology and accelerating the development of medicines.
Cell - a Cell Press journal
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Now online! A pseudoenzyme sensor of trehalose-6-phosphate directly represses the metabolic integrator SnRK1 in plants

dlvr.itA pseudoenzyme sensor of trehalose-6-phosphate directly represses the metabolic integrator SnRK1 in plantsIn Arabidopsis, pseudoenzyme class II T6P synthase functions as a T6P sensor that directly represses the master metabolic regulator SnRK1, highlighting a conserved switch that couples carbon availability to metabolic homeostasis in plants.
Cell - a Cell Press journal
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Now online! Mechanisms of transcription control by distal enhancers from single-gene nanoscopy

dlvr.itMechanisms of transcription control by distal enhancers from single-gene nanoscopyHigh-resolution real-time imaging of enhancer-promoter communication reveals how the two genomic loci are actively brought together through cohesin-mediated loop extrusion and how E-P interactions are temporally coordinated with transcriptional bursts. Unexpectedly, components of the RNA Pol II general machinery form nanoscale clusters at distal enhancers, and embedding the promoter into such clusters boosts GTF activities and triggers burst initiation.
Cell - a Cell Press journal
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Now online! PTPRS mediates invasion of tetanus neurotoxin into the central nervous system

dlvr.itPTPRS mediates invasion of tetanus neurotoxin into the central nervous systemTetanus neurotoxin enters the central nervous system through motor neurons. This study identifies PTPRS as the long-sought retrograde transport receptor that directs toxin trafficking in motor neurons into the spinal cord, uncovering a host pathway that can be targeted for post-exposure treatment and for drug delivery into the central nervous system.
Cell - a Cell Press journal
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Now online! A high-dimensional population code in the bat motor cortex during natural dexterous flight

dlvr.itA high-dimensional population code in the bat motor cortex during natural dexterous flightBats use their hand-like wings to reproduce natural flights with wingbeat-level precision. Rather than mainly tracking the wingbeat cycle, the wing motor cortex generates sparse, distinct population states with little shared variance across wingbeats, resulting in a high-dimensional code distinct from that typically observed in constrained tasks.

Cell - a Cell Press journal reposted

Max Planck Institute for Plant Breeding Research
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πŸ“£Paper Alert! πŸ₯³ A new study @cp-cell.bsky.social from the Schulze-Lefert group @mpipz.bsky.social reveals how Arabidopsis adapts its iron acquisition strategy to soil pH, using coumarins & bacterial pathways to access this essential nutrient. πŸ‘ πŸ‘‰ bit.ly/4yEU9Em #plantsci www.cell.com/cell/fulltex...

cell.comArabidopsis uses distinct coumarins and bacterial pathways for pH-adaptive iron acquisitionArabidopsis coordinates Fe acquisition with its root microbiota by releasing distinct coumarin chemotypes in response to environmental pH. These root-exuded specialized metabolites interact with root-...
Cell - a Cell Press journal
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Now online! A fluctuation test for gastruloid heterogeneity

dlvr.itA fluctuation test for gastruloid heterogeneityOrganoids grown side by side under identical conditions vary unpredictably, a longstanding obstacle to their use. Adapting the logic of a classic fluctuation test to gastruloids grown from single stem cells shows that this variability is largely inherited rather than induced and is traceable to fluctuations in the state of the founding cell.
Cell - a Cell Press journal
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Now online! Comprehensive lineage tracing maps the landscape of cell fate decisions in mouse embryogenesis

dlvr.itComprehensive lineage tracing maps the landscape of cell fate decisions in mouse embryogenesisWe use PEtracer to reconstruct high-resolution lineage histories for >1.4 million cells from E7.5 to E10.0 during mouse development, providing a quantitative view of fate bias, restriction timing, and clonal output. Across diverse tissues, these data reveal highly reproducible lineage architectures and define general and tissue-specific strategies of cell fate specification.
Cell - a Cell Press journal
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Now online! Immunoregulatory gene GIMAP6 suppresses lethal atherosclerotic vasculopathy and ischemic heart failure

dlvr.itImmunoregulatory gene GIMAP6 suppresses lethal atherosclerotic vasculopathy and ischemic heart failureBy destabilizing the endothelium and promoting macrophage lipid loading and inflammation, GIMAP6 deficiency drives atherosclerosis and ischemic heart disease through a mechanism that operates without hyperlipidemia, yet hyperlipidemia significantly exacerbates disease progression.
Cell - a Cell Press journal
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Now online! Arabidopsis uses distinct coumarins and bacterial pathways for pH-adaptive iron acquisition

dlvr.itArabidopsis uses distinct coumarins and bacterial pathways for pH-adaptive iron acquisitionArabidopsis coordinates Fe acquisition with its root microbiota by releasing distinct coumarin chemotypes in response to environmental pH. These root-exuded specialized metabolites interact with root-associated bacteria to mobilize Fe either through bacterial siderophore-dependent chelation at circumneutral pH or through bacterial redox-sensing-controlled reduction at acidic pH.
Cell - a Cell Press journal
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Now online! STING reprogramming by estrogen promotes neutrophil extracellular trap formation and sex-biased resistance to ADC therapy

dlvr.itSTING reprogramming by estrogen promotes neutrophil extracellular trap formation and sex-biased resistance to ADC therapySex differences in antibody-based cancer therapy remain poorly understood. This study identifies estrogen-driven STING reprogramming and neutrophil extracellular trap formation as a mechanism of functional antigen shielding that limits ADC efficacy.
Cell - a Cell Press journal
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Now online! SPARCS enables scalable recovery of complex image-based phenotypes for genetic screening

dlvr.itSPARCS enables scalable recovery of complex image-based phenotypes for genetic screeningCurrent genetic screens face a trade-off between scaling to large mutant libraries and measuring information-rich phenotypes. SPARCS automates laser microdissection to enable pooled forward genetic screens for complex image-based phenotypes at scale. By physically recovering individual mutants, SPARCS supports multimodal profiling of hits beyond genotyping, including via mass spectrometry-based proteomics.
Cell - a Cell Press journal
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Now online! Cancer competition for vitamin B2 creates metabolic checkpoint for T cell ferroptosis

dlvr.itCancer competition for vitamin B2 creates metabolic checkpoint for T cell ferroptosisA CRISPR screen of solute carriers reveals that T cells depend on SLC52A3 for VB2 uptake, whereas tumors preferentially exploit SLC52A2 to outcompete them, thereby driving T cell ferroptosis. Enforced SLC52A3 overexpression in T cells reverses this metabolic competition and enhances their antitumor activity.