Cell Reports

Cell Reports

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Cell Reports, published by Cell Press, is a weekly open-access journal that publishes high-quality papers across the entire life sciences spectrum.

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Cell Reports
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LiP-MS reveals a feedback loop of tomato UDP-glucosyltransferases managing bioactive jasmonate homeostasis

dlvr.itLiP-MS reveals a feedback loop of tomato UDP-glucosyltransferases managing bioactive jasmonate homeostasisVenegas-Molina et al. demonstrate the utility of limited proteolysis-coupled mass spectrometry (LiP-MS) for the discovery of plant metabolite-binding proteins by identifying enzymes that glycosylate the plant hormone jasmonic acid in tomato. Glycosylation leads to partial attenuation of hormone activity, indicating that these enzymes participate in jasmonic acid catabolism.
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Myeloperoxidase and anti-MPO IgG synergistically enhance TLR9-mediated immune activation in ANCA-associated vasculitis

dlvr.itMyeloperoxidase and anti-MPO IgG synergistically enhance TLR9-mediated immune activation in ANCA-associated vasculitisAnti-myeloperoxidase (MPO) IgG drives ANCA-associated vasculitis by activating neutrophils. Krollmann et al. demonstrate that, beyond neutrophil activation, anti-MPO IgG facilitates TLR9-dependent DNA sensing in murine GM-CSF-derived bone marrow myeloid cells and human pDCs, establishing a role for ANCAs in inducing pathogenic nucleic acid immunity.
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DDX39A unwinds viral RNA G-quadruplexes to limit α-Synuclein amyloidogenesis

dlvr.itDDX39A unwinds viral RNA G-quadruplexes to limit α-Synuclein amyloidogenesisJain et al. demonstrate that RNA helicase DDX39A regulates α-Synuclein amyloidogenesis by unwinding RNA G-quadruplexes (rG4s) and that viral rG4s accelerate this aggregation by perturbing α-Synuclein-DDX39A interaction equilibrium. They further show that α-Synuclein reciprocally enhances DDX39A helicase activity through co-condensation, proposing a mechanistic link between viral infections and Parkinson’s disease.
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FluxAtlas is a pan-cancer metabolic flux atlas that identifies tumor-selective dependencies and prognostic biomarkers

dlvr.itFluxAtlas is a pan-cancer metabolic flux atlas that identifies tumor-selective dependencies and prognostic biomarkersKohli et al. apply enzyme- and nutrient-constrained genome-scale modeling to more than 10,000 tumors across 28 cancer types, defining a pan-cancer metabolic-flux landscape. This analysis reveals tissue-specific metabolic adaptations and vulnerabilities, including bile acid-linked redox and lipid rewiring, renal-specific purine dependence, and flux-based survival predictors, such as biotin uptake.
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Increased extracellular fluid viscosity drives M2-like macrophage polarization to promote breast cancer progression and immunotherapy resistance

dlvr.itIncreased extracellular fluid viscosity drives M2-like macrophage polarization to promote breast cancer progression and immunotherapy resistanceZhang et al. demonstrate that increased extracellular fluid viscosity promotes immunosuppressive M2-like macrophage polarization through integrin/FAK-STAT3 signaling and cytoskeletal remodeling. This viscosity-driven macrophage state accelerates breast cancer progression and reduces the response to anti-PD-1 immunotherapy, linking a physical property of the tumor microenvironment to immune evasion.
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A bifunctional ARHGEF17-AS1 locus encodes MSEP, a protein that supports mitotic spindle organization

dlvr.itA bifunctional ARHGEF17-AS1 locus encodes MSEP, a protein that supports mitotic spindle organizationMahale et al. identify MSEP, a protein encoded within the ARHGEF17-AS1 antisense locus, and show that it localizes to the mitotic spindle and supports spindle organization through a TPX2-associated pathway. The work reveals distinct RNA- and protein-associated outputs from a single bifunctional genomic locus.
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Biased connectivity shapes food odor categorization in the Drosophila mushroom body

dlvr.itBiased connectivity shapes food odor categorization in the Drosophila mushroom bodyChan et al. show that individual Kenyon cell types in the Drosophila associative learning center, the mushroom body, encode odors according to different principles. Biased projection-neuron input yields food-related odor representations by αβ Kenyon cells that support the categorization of food odors in addition to their discrimination.
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Cell volume regulation in metazoans involves phosphorylation of TSC22D proteins

dlvr.itCell volume regulation in metazoans involves phosphorylation of TSC22D proteinsLee et al. describe a condensate-based signaling mechanism regulating cell volume homeostasis. TSC22D, WNK, and NRBP proteins form dynamic condensates that modulate WNK-SPAK/OSR1 signaling. WNK-dependent phosphorylation of NRBP1 and TSC22D2 promotes pathway activation and condensate dissolution. These findings support a model where TWN bodies behave as signaling assemblies for osmo-regulation.
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MCUB restricts mitochondrial calcium to support metabolic adaptation and homeostasis in glioblastoma

dlvr.itMCUB restricts mitochondrial calcium to support metabolic adaptation and homeostasis in glioblastomaSun et al. find that hypoxia-induced MCUB promotes a restricted mitochondrial Ca2+ flux state that supports metabolic adaptation and mitochondrial homeostasis in glioblastoma. Targeting MCUB-dependent calcium gating exerts antitumor effects and enhances radiosensitivity, revealing this mechanism as a potential therapeutic vulnerability.
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Matrix viscoelasticity amplifies pro-fibrotic crosstalk between cardiac fibroblasts and macrophages

dlvr.itMatrix viscoelasticity amplifies pro-fibrotic crosstalk between cardiac fibroblasts and macrophagesMatrix viscoelasticity governs cardiac fibroblast-macrophage crosstalk, with soft, viscous environments amplifying profibrotic signaling through dynamic paracrine feedback. Atcha et al. examine how mechanical cues and sequential immune activation synergize to recapitulate post-infarction fibrosis, identifying cytokine networks that may serve as therapeutic targets in cardiac remodeling.
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Placental trophoblasts exhibit iron dysregulation and ferroptosis signaling associated with SARS-CoV-2 restriction

dlvr.itPlacental trophoblasts exhibit iron dysregulation and ferroptosis signaling associated with SARS-CoV-2 restrictionMcColl et al. demonstrate that SARS-CoV-2 impairs placental iron efflux, leading to persistent iron accumulation and impaired maternal-fetal iron transfer, and activates ferroptosis signaling, which may limit viral replication. This uncovers both a novel antiviral role of ferroptosis in the placenta and a new mechanism for adverse pregnancy outcomes associated with COVID-19.
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Topoisomerase I inhibition yields a CD74high/MHChigh human microglial subtype with enhanced Aβ uptake

dlvr.itTopoisomerase I inhibition yields a CD74high/MHChigh human microglial subtype with enhanced Aβ uptakeCamptothecin and its analog Topotecan drive human microglia toward a CD74high/MHChigh state with enhanced amyloid-β phagocytosis and altered inflammatory signaling. Using cell, organoid, and zebrafish models, Haage et al. link a transcriptomic microglial subtype to distinct functional properties, uncovering a pharmacological route to model microglial states implicated in neurodegeneration.
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piRNA-mediated silencing of exogenous retrovirus in mouse spermatogonial stem cells

dlvr.itpiRNA-mediated silencing of exogenous retrovirus in mouse spermatogonial stem cellsShiromoto et al. show that PIWI-interacting RNAs and TRP53 protect mouse spermatogonial stem cells from exogenous retroviral infection. Disruption of this pathway enhances viral expression and germline transmission following testicular infection, revealing a mechanism that preserves genome integrity across generations.
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Dietary α-ketoglutarate modulates lung adenocarcinoma growth and epigenetic remodeling in a sex-dependent fashion

dlvr.itDietary α-ketoglutarate modulates lung adenocarcinoma growth and epigenetic remodeling in a sex-dependent fashionAlcaraz Jr. et al. show that dietary supplementation with calcium-αKG modulates lung cancer epigenetics and transcriptional programs in a sex-dependent way, resulting in reduced tumor growth in females but increased tumor growth in males.
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Alternate day fasting attenuates metabolic dysfunction-associated arterial thrombotic risk via increasing indole-3-propionic acid

dlvr.itAlternate day fasting attenuates metabolic dysfunction-associated arterial thrombotic risk via increasing indole-3-propionic acidFeng et al. show that alternate day fasting attenuates metabolic dysfunction-associated arterial thrombosis by gut microbiota reshaping. They identify the microbial metabolite indole-3-propionic acid as a crucial contributor that suppresses platelet activation and thrombosis by maintaining intraplatelet Rho GTPase cycle homeostasis, with reduced circulating levels observed in affected patients.
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Structured and target-specific development of cortico-cortical connectivity in the mouse visual cortex

dlvr.itStructured and target-specific development of cortico-cortical connectivity in the mouse visual cortexJacobs and Ratliff et al. show how V1 wiring to eleven higher visual areas develops in mouse cortex through directed, region-specific targeting: medial areas innervate early and refine gradually into adulthood, while lateral areas overshoot early and prune to adult levels by P24. Feedforward and feedback circuits emerge concurrently.
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SDCBP competes with CBL to stabilize PES1 and promote c-Myc translation in ESCC tumorigenesis

dlvr.itSDCBP competes with CBL to stabilize PES1 and promote c-Myc translation in ESCC tumorigenesisXiao et al. demonstrate that SDCBP drives esophageal squamous cell carcinoma progression by preventing CBL-mediated ubiquitination and degradation of PES1. Stabilized PES1 enhances pre-rRNA processing and promotes c-Myc protein synthesis. Tumor-targeted delivery of SDCBP antisense oligonucleotides effectively suppresses tumor growth.
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A USP28-BRD4 axis contributes to the acceleration of breast cancer growth by hyperglycemia

dlvr.itA USP28-BRD4 axis contributes to the acceleration of breast cancer growth by hyperglycemiaHow diabetes promotes cancer progression remains poorly understood. Li et al. show that high blood glucose stabilizes a cancer-promoting protein, BRD4, through a molecular switch involving USP28 and SIRT1. This USP28-BRD4 axis links hyperglycemia to breast cancer progression and may offer therapeutic insights.
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A compact Druantia defense clears phage infections via single-stranded DNA recognition and directional duplex unwinding

dlvr.itA compact Druantia defense clears phage infections via single-stranded DNA recognition and directional duplex unwindingHimpich et al. show how the Druantia III-A defense system detects and fends off invading phage DNA. The DruE component recognizes exposed single-stranded DNA and unwinds flanking duplex regions 3′-to-5′, employing unique lock, wedge, and clamp elements, while the DruH component might scaffold DruE and host proteins that dissociate upon infection.
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The spindle-associated antisense RNA ARHGEF17-AS1 functionally contributes to mitotic spindle integrity

dlvr.itThe spindle-associated antisense RNA ARHGEF17-AS1 functionally contributes to mitotic spindle integrityMahale et al. identify ARHGEF17-AS1 as a spindle-associated antisense RNA that contributes to mitotic spindle integrity. The RNA associates with RPS3 and dynein, supports extra-ribosomal RPS3 abundance and spindle recruitment, and is linked to RNF10-dependent RPS3 monoubiquitination during mitosis.
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An amygdaloreticular pathway promotes motor programs of ingestion

dlvr.itAn amygdaloreticular pathway promotes motor programs of ingestionLafferty et al. show that a collateralized amygdala projection to the hindbrain can drive context-dependent consummatory motor states. Activity in this pathway correlates with the motor action of licking, and stimulating this pathway promotes ingestion-related behaviors toward food and non-food objects, providing a potential mechanism for ingestion beyond homeostatic need.
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Processing of lysophosphatidylcholines by ExoU secreted by P. aeruginosa leads to inflammasome activation and cell death

dlvr.itProcessing of lysophosphatidylcholines by ExoU secreted by P. aeruginosa leads to inflammasome activation and cell deathPseudomonas aeruginosa alters the lipidome of host cells by injecting the toxin ExoU, causing lysophosphatidylcholine accumulation that activates inflammatory pathways and inflammasome-mediated cell death. This response is inhibited by lysophosphatidylcholine acyltransferase 3. In patients with cystic fibrosis, the expression of ExoU is reduced, promoting immune evasion and chronic infection.
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Mycn facilitates hematopoietic stem and progenitor cell generation from endothelial cells by inhibiting adhesion signaling

dlvr.itMycn facilitates hematopoietic stem and progenitor cell generation from endothelial cells by inhibiting adhesion signalingWang et al. demonstrate that Mycn expression is initiated in hemogenic endothelial cells to promote hematopoietic stem and progenitor cell generation in mouse embryos. Mycn acts by inhibiting endothelial adhesion signaling to enable the endothelial-to-hematopoietic transition.
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PADI-dependent mitochondrial adaptation drives resistance to KRAS inhibitors

dlvr.itPADI-dependent mitochondrial adaptation drives resistance to KRAS inhibitorsKRAS-mutant pancreatic and colorectal cancers frequently develop resistance to KRAS(ON) and KRAS(OFF) inhibitors. Here, Gani et al. identify a PADI-dependent adaptive circuit that promotes therapeutic escape through HSPA9/Mortalin citrullination. Pharmacological PADI inhibition restores KRAS inhibitor sensitivity and induces non-lytic apoptosis, revealing a therapeutic vulnerability in KRAS-driven tumors.
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Antigenic landscape of rabies and related lyssaviruses revealed by cryo-EM

dlvr.itAntigenic landscape of rabies and related lyssaviruses revealed by cryo-EMCallaway et al. solve cryo-EM structures of nine antibodies in complex with rabies virus glycoprotein, illustrating the breadth of the rabies antibody-binding landscape. Two identified antigenic sites, sites V and VI, are unusually well conserved across rabies and related lyssaviruses and are targets for structure-guided antibody and vaccine design.
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Theta synchronization coordinates ventral temporal and medial temporal coding of human face familiarity

dlvr.itTheta synchronization coordinates ventral temporal and medial temporal coding of human face familiarityLi et al. reveal how the human brain recognizes familiar faces by coordinating visual perception and memory through theta-frequency synchronization. Their findings show that rhythmic neural activity links feature representations in the visual cortex with memory signals in the medial temporal lobe, providing a mechanistic framework for processing face familiarity.
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The left PBN to aCM pathway mediates pain-related aversion in male mice

dlvr.itThe left PBN to aCM pathway mediates pain-related aversion in male miceYan et al. show that in male mice, the left parabrachial nucleus (L-PBN), but not its right counterpart (R-PBN), modulates formalin-induced conditioned place aversion (F-CPA) through direct projections to the anterior central thalamus nucleus (aCM). In contrast, neither L-PBN nor R-PBN is involved in F-CPA control in female mice.
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Anticipatory metabolic regulation drives the distinct and improved metabolic state of caloric restriction compared to Fasting-Refeeding cycles

dlvr.itAnticipatory metabolic regulation drives the distinct and improved metabolic state of caloric restriction compared to Fasting-Refeeding cyclesVelingkaar et al. demonstrate that metabolic adaptation during caloric restriction is driven by more than prolonged fasting. They show that caloric restriction engages anticipatory, circadian-regulated metabolic programs independent of gastric emptying, whereas fasting-refeeding cycles remain nutrient-driven, disrupting circadian rhythmicity while impairing glucose tolerance and promoting hepatic lipid accumulation.
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Colony morphogenesis regulates sporulation dynamics in bacterial biofilms

dlvr.itColony morphogenesis regulates sporulation dynamics in bacterial biofilmsJones et al. show how the growth dynamics of bacterial biofilms regulate the distribution of dormant spore production within colonies. Cells are rapidly driven to dormancy by a wave of sporulation sweeping through biomass, but increasing the rate of colony spreading proportionally slows the transition to dormancy.
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A CsWRKY46-CsPBL9-CsARI1 tripartite regulatory module coordinates H2O2 production and callose deposition in citrus fruit immunity

dlvr.itA CsWRKY46-CsPBL9-CsARI1 tripartite regulatory module coordinates H2O2 production and callose deposition in citrus fruit immunityXu et al. reveal a tripartite and interactive rheostat orchestrating self-linked immune responses in citrus fruit, elucidating the poorly understood regulatory mechanisms of callose deposition in plant immunity. Notably, E3 ligase CsARI1 acts as an immune brake via both ubiquitination-dependent and non-catalytic pathways, expanding the functions of RBR-type E3 ligases.
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Albumin uptake through FcRn promotes tumor-associated macrophage maturation and albumin-bound immunotherapy response

dlvr.itAlbumin uptake through FcRn promotes tumor-associated macrophage maturation and albumin-bound immunotherapy responseHu et al. show that myeloid FcRn substantially supports tumor albumin accumulation and Nrf2-dependent macrophage maturation. Circulating albumin is associated with relative macrophage abundance in clinical tumor specimens, and an albumin-conjugated STING agonist leverages this biology to activate tumor myeloid cells and improve antitumor activity in mouse models.
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Spontaneous lytic reactivation drives a persistent B cell-vector pathway for epithelial dissemination of the Epstein-Barr virus

dlvr.itSpontaneous lytic reactivation drives a persistent B cell-vector pathway for epithelial dissemination of the Epstein-Barr virusVo et al. reveal that EBV-infected B cells serve as efficient cellular vehicles for viral dissemination to epithelial cells. This contact-dependent transfer requires spontaneous lytic reactivation, genome-containing virion production, and epithelial receptors, including EphA2, DSC2, and R9AP, offering a mechanistic framework for understanding strain tropism and host-virus interactions.
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MG53 suppresses IRF7 to reprogram macrophages and promote antitumor immunity in pancreatic ductal adenocarcinoma

dlvr.itMG53 suppresses IRF7 to reprogram macrophages and promote antitumor immunity in pancreatic ductal adenocarcinomaPei et al. show that macrophage MG53 suppresses IRF7 to promote pro-inflammatory macrophage and T cell responses, while MG53 deficiency drives immunosuppressive polarization. Low-MG53/high-IRF7 TAMs correlate with poor survival in PDAC and CRC. MG53 mRNA-LNP reprograms the TME and suppresses pancreatic tumor growth, suggesting a promising immunotherapy.
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IL-15 signaling during a critical NK cell developmental window subverts maturation and KIR acquisition

dlvr.itIL-15 signaling during a critical NK cell developmental window subverts maturation and KIR acquisitionRuesch et al. demonstrate that during in vitro human natural killer cell development, early-stage exposure to interleukin-15 paradoxically subverts key aspects of maturation. Their experimental findings mirror those seen in patients receiving hematopoietic stem cell transplants, suggestive of a similar mechanism contributing to delayed natural killer cell maturation in vivo.
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Fungal lipase LipA disarms macrophages by remodeling their lipidome, enabling full virulence in immunocompetent hosts

dlvr.itFungal lipase LipA disarms macrophages by remodeling their lipidome, enabling full virulence in immunocompetent hostsGoldman et al. show that Aspergillus fumigatus lipase LipA remodels the macrophage lipidome, suppressing pro-inflammatory eicosanoid signaling and immune clearance. By depleting host lipid precursors, LipA promotes fungal survival and is required for full virulence in immunocompetent hosts.
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Temporal CRAC channel blockade modulates the MYC-MXD axis to attenuate autoimmune inflammation

dlvr.itTemporal CRAC channel blockade modulates the MYC-MXD axis to attenuate autoimmune inflammationTemporal CRAC channel inhibition disrupts Th17 cell effector function and metabolic programming. Wu et al. reveal a CRAC-MYC-MXD regulatory axis essential for sustaining Th17 identity, demonstrating that temporal blockade of CRAC channels attenuates pathogenic Th17 responses in both mouse models of autoimmunity and human cells.
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Defensive lipid droplets are PUFA reservoirs and suppliers driving bacterial clearance and inflammation

dlvr.itDefensive lipid droplets are PUFA reservoirs and suppliers driving bacterial clearance and inflammationWhen infected by bacteria, viruses, or parasites, eukaryotic cells accumulate lipids in organelles called lipid droplets. Bosch et al. investigate the identity and defensive roles of these lipids. In activated macrophages, lipid droplets collect and deliver ω-6 and ω-3 polyunsaturated fatty acids to mediate bacterial phagocytosis and inflammation.
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ENPP1 buffers extracellular cGAMP in brown adipose tissue to limit insulin resistance

dlvr.itENPP1 buffers extracellular cGAMP in brown adipose tissue to limit insulin resistanceNutritional excess triggers mitochondrial DNA leakage in brown adipocytes, promoting the production and release of the immunotransmitter cGAMP into the extracellular space. Wang et al. discover that ENPP1 acts as a vital immunometabolic checkpoint by clearing this extracellular cGAMP pool, thereby preventing local tissue inflammation, insulin resistance, and diet-induced obesity.