Phage-related symbiosis and antagonism shape gut ecosystem dynamics in Lachnospiraceae and Bacteroidaceae Zhao et al. develop cMECOS to recover 5,006 HMQ MAGs and reveal two gut bacterial networks linked to temperate/virulent phages, which are disrupted in IBD and obesity. These phage-related networks regulate gut homeostasis, offering insights for microbiome-targeted therapies.

Phage-related symbiosis and antagonism shape gut ecosystem dynamics in Lachnospiraceae and Bacteroidaceae

4-octyl itaconate inhibits cytokine-mediated inflammation via alkylation of TYK2 and JAK1 Li et al. discovered that 4-octyl itaconate (4-OI) directly covalently modifies TYK2 and JAK1 to inhibit the type I interferon response. Endogenous metabolite itaconate in sepsis is a JAK inhibitor. In the mouse, in vivo experiments, intraperitoneal injection of 4-octyl itaconate could alleviate multi-organ damage caused by sepsis.

4-octyl itaconate inhibits cytokine-mediated inflammation via alkylation of TYK2 and JAK1

Targeting systemic and tumor metabolic balances with ketogenic diets enhance efficacy of therapy in FLT3-ITD acute myeloid leukemia Goupille et al. describe an alternative approach targeting the host and tumoral primary metabolism in FLT3-mutant leukemia. Ketogenic diet strategies aiming to imbalance lipid homeostasis augment fatty acid and amino acid degradative activity, attenuating FLT3 signaling activation, cell proliferation, and leukemia progression upon targeted therapies.

Targeting systemic and tumor metabolic balances with ketogenic diets enhance efficacy of therapy in FLT3-ITD acute myeloid leukemia

Sexual dimorphism shapes renal metabolic adaptation to a ketogenic diet By tracking metabolites entering and leaving the kidney in mice, Kelly et al. uncovered strong sex differences in kidney metabolism under normal and ketogenic diets. Female kidneys showed unexpected increases in sugar and ketone production on a ketogenic diet, highlighting sex as an important factor in kidney health and disease.

Sexual dimorphism shapes renal metabolic adaptation to a ketogenic diet

RNA binding as an emerging regulatory dimension in the type I IFN response Iselin et al. explore how the type I IFN response regulates RNA-binding activity using RNA-interactome capture and extend the RIC protocol to assess the role of phosphorylation in this process. Focusing on MATR3, they highlight how this protocol extension, phospho-RIC, can be used to identify PTM-driven regulatory events.

RNA binding as an emerging regulatory dimension in the type I IFN response

Slc2a6 in Kupffer cells shapes host recognition of Streptococcus pneumoniae Ding et al. demonstrate that the metabolic transporter Slc2a6 in Kupffer cells restrains early immune recognition of Streptococcus pneumoniae. Loss of Slc2a6 enhances natural-antibody-mediated bacterial capture in the liver, revealing a link between metabolism, innate immunity, and bacterial infection control.

Slc2a6 in Kupffer cells shapes host recognition of Streptococcus pneumoniae

Glymphatic influx is negatively correlated with cerebral blood volume in male mice Li et al. use multimodal MRI to show that cerebral blood volume is inversely correlated with glymphatic influx across six brain states. Lower CBV is associated with expanded extra-ventricular CSF space, and caffeine produces a similar pattern in awake mice, suggesting CBV as a tonic vascular factor complementing pulsation and vasomotion.

Glymphatic influx is negatively correlated with cerebral blood volume in male mice

Regulation of neuronal invasion of small cell lung cancer by STMN2/β-alanine-controlled metabolic reprogramming Zhou et al. demonstrate that perineural invasion (PNI) is an adverse prognostic factor in small cell lung cancer. They identify a neuron-STMN2-β-alanine axis, where the neural microenvironment upregulates STMN2 in tumor cells, reprogramming β-alanine metabolism to enhance cell migration and drive neural invasion, revealing a potential therapeutic target.

Regulation of neuronal invasion of small cell lung cancer by STMN2/β-alanine-controlled metabolic reprogramming

ABA signaling is involved in the regulation of BSK1 stability mediated by the UBP24-PUB25/26 module in Arabidopsis Li et al. report that Arabidopsis BSK1 negatively regulates ABA signaling. The stability of BSK1 is dynamically controlled by PUB25 and PUB26, a process likely regulated by BAK1 phosphorylation, whereas UBP24 stabilizes BSK1 by removing ubiquitin chains. ABA shifts this balance toward degradation by inducing the accumulation of PUB25/26.

ABA signaling is involved in the regulation of BSK1 stability mediated by the UBP24-PUB25/26 module in Arabidopsis

Polyglutamine homorepeat regulates Runx2 condensation and cellular localization in a KPNA3-dependent manner Weng et al. investigate the function of polyglutamine (polyQ) in Runx2, demonstrating that the deletion of the polyQ repeat disrupts the interaction with KPNA3. This impairs the steric blocking effects of KPNA3 on Runx2 condensation. They revealed the unique role of polyQ repeat in modulating the liquid-like state of Runx2.

Polyglutamine homorepeat regulates Runx2 condensation and cellular localization in a KPNA3-dependent manner

Regulatory T cell-derived TGF-β signaling governs the differentiation and maintenance of tumor-infiltrating bystander CD8+ T cells Lin et al. reveal that tumor-infiltrating bystander CD8+ T cells are heterogeneous and undergo a TCM-to-TEM-to-TRM differentiation trajectory driven by Treg-derived TGF-β signaling through suppression of KLF2. This mechanism sustains bystander CD8+ T cell heterogeneity and accumulation in tumors and provides a targetable mechanism for cancer immunotherapy.

Regulatory T cell-derived TGF-β signaling governs the differentiation and maintenance of tumor-infiltrating bystander CD8+ T cells

Optogenetic mediated contractility enables reversible control of microglial morphology and migration in vivo Biermeier et al. use live imaging in zebrafish to show that microglia alternate between distinct morphological states that support brain surveillance and phagocytosis. By optogenetically controlling cytoskeletal contractility, they demonstrate programmable, reversible control of microglial behavior in the living brain.

Optogenetic mediated contractility enables reversible control of microglial morphology and migration in vivo

Condensation of an H3K9me3 methyltransferase complex promotes heritable gene silencing and heterochromatin formation Cai et al. report that repetitive genomic sequences promote the formation of condensates containing the H3K9me3 methyltransferase SET-25 and its cofactors SECP-1 and SECP-2. This process is required for preferential heterochromatin formation and heritable gene silencing in Caenorhabditis elegans.

Condensation of an H3K9me3 methyltransferase complex promotes heritable gene silencing and heterochromatin formation

STUB1-VCP/p97 complex regulates mitophagy via fine-tuning of PINK1 levels Lin et al. discover that the STUB1-VCP axis mediates the ubiquitination and degradation of full-length PINK1 upon mitochondrial damage, a critical mechanism that fine-tunes PINK1 levels to ensure efficient mitophagy. This fine-tuning mechanism is impaired in Alzheimer’s disease, and its loss disrupts associated learning capability in C. elegans.

STUB1-VCP/p97 complex regulates mitophagy via fine-tuning of PINK1 levels

Hyperdiploidy impairs fetal hematopoietic progenitor fitness and differentiation enabling persistence of rare preleukemic aneuploid clones Thampi et al. model prenatal hyperdiploidy in human fetal hematopoietic stem/progenitor cells and show that aneuploidy impairs fitness and delays differentiation. Although hyperdiploid cells are outcompeted in vitro, rare clones persist in vivo with cB-ALL-like chromosomal gains but fail to initiate leukemia, supporting a two-step leukemogenesis model.

Hyperdiploidy impairs fetal hematopoietic progenitor fitness and differentiation enabling persistence of rare preleukemic aneuploid clones

Schizophrenia-associated complement C4 impairs synaptic connectivity and decreases microglia-synapse interactions through CR3 signaling Genetic risk for schizophrenia has been linked to high expression of complement C4, but the mechanism remained unclear. Gockel et al. show that microglial CR3 receptors mediate the effects of elevated C4 expression in the mouse cortex, including altered synapse density and function, decreased microglial motility, and reduced microglia-neuron contacts.

Schizophrenia-associated complement C4 impairs synaptic connectivity and decreases microglia-synapse interactions through CR3 signaling

The maternal-fetal interface as an immunological barrier: Structure, regulation, and breakdown The maternal-fetal interface is a specialized immunological barrier that integrates tolerance, defense, and regulated inflammation throughout gestation. Distinct immune populations mediate implantation, immune homeostasis, and parturition, while dysregulation can result in chronic placental inflammation, a consequence of barrier failure, characterized by infiltration of maternal T cells into placental/fetal tissues.

The maternal-fetal interface as an immunological barrier: Structure, regulation, and breakdown

Genome-wide identification and characterization of QTLs for transcriptional noise in human midbrain cells Hirose et al. created a genome-wide resource of transcriptional noise QTLs (tnQTLs) in human iPSC-derived midbrain cells. One-fifth of these tnQTLs lack eQTL effects and show distinct enrichment patterns in cis-regulatory elements and human complex-trait-associated loci, unraveling roles of transcriptional noise and their regulators in biology and disease.

Genome-wide identification and characterization of QTLs for transcriptional noise in human midbrain cells

Mutation elevation and functional alterations in Escherichia coli are pertinent to the onset of gestational diabetes mellitus Zheng et al. reveal that during pregnancy, relaxed purifying selection in the gut enables mutation accumulation in Escherichia coli. This strain-level genomic plasticity, uncoupled from taxonomic abundance, leads to functional alterations and ecological disruptions that are linked to the subsequent development of gestational diabetes mellitus.

Mutation elevation and functional alterations in Escherichia coli are pertinent to the onset of gestational diabetes mellitus

Gcn2 deficiency triggers anemia and hypoxic intolerance in zebrafish Liu et al. show that the integrated stress response kinase GCN2 is essential for hypoxic adaptation by maintaining iron and redox homeostasis. Using zebrafish and human cell models, they find that GCN2 deficiency disrupts iron metabolism, sensitizes cells to ferroptosis, and contributes to anemia under hypoxic stress.

Gcn2 deficiency triggers anemia and hypoxic intolerance in zebrafish

RUNX2 and USP16 stabilize MFRN2 to maintain pulmonary epithelial barrier integrity in sepsis-induced acute lung injury Lai et al. demonstrate that a RUNX2-USP16-MFRN2 axis drives epithelial ferroptosis in sepsis-induced acute lung injury by disrupting mitochondrial homeostasis, suggesting a therapeutic target for enhancing lung resilience.

RUNX2 and USP16 stabilize MFRN2 to maintain pulmonary epithelial barrier integrity in sepsis-induced acute lung injury

Methionine metabolism is linked with phospholipid and glutamine metabolism to drive ferroptosis Kim et al. identify methionine as a key determinant of cystine deprivation-induced ferroptosis. Methionine depletion diverts glutamine into the glutamine-methionine bi-cycle and triggers ACSL4 proteasomal degradation, reducing ROS and PUFA incorporation into PLs. SAM supplementation restores metabolic state and ferroptosis sensitivity.

Methionine metabolism is linked with phospholipid and glutamine metabolism to drive ferroptosis

Non-gonadal PIWIL1/Aubergine drives regenerative and tumorigenic stem cell proliferation and tumorigenesis in the intestine Expression and function of classical germline genes are reported in somatic tissues. Bellec et al. report damage-inducible upregulation and function of the PIWI protein Aubergine in regenerating intestinal stem cells. Roles of Aubergine in the adult intestine involve translation of essential stem cell factors and are uncoupled from piRNA regulation.

Non-gonadal PIWIL1/Aubergine drives regenerative and tumorigenic stem cell proliferation and tumorigenesis in the intestine

Ecological specialization and admixture drive the genomic and phenotypic diversity in Yarrowia lipolytica Izquierdo-Gea et al. analyze a worldwide collection of 126 Yarrowia lipolytica strains to show how ecological specialization and gene flow between populations shape genomes and traits. By combining genomics and phenotypes, the study provides a powerful resource to connect natural diversity with industrially relevant traits and guide targeted microbial bioprospecting.

Ecological specialization and admixture drive the genomic and phenotypic diversity in Yarrowia lipolytica

Cellular fitness is determined by ribosomal protein S12-mediated release of a truncated Xrp1 Kakemura et al. show that Xrp1, a key determinant of cell competition, is abundantly expressed in normal cells, but it is not translated due to an upstream ORF. They show that unfit “loser” cells cause splicing-mediated skipping of the uORF via RpS12, which generates a truncated Xrp1 protein that causes cell death.

Cellular fitness is determined by ribosomal protein S12-mediated release of a truncated Xrp1

Cellular and subcellular specialization enables biology-constrained deep learning Galloni et al. introduce “dendritic target propagation”: a Dale’s law-compliant learning algorithm for cortical microcircuits with soma- and dendrite-targeting inhibition and realistic connectivity constraints. By combining experimentally derived BTSP and Hebbian rules, dendrites compute local error proxies via E/I mismatch, supporting gradient-based deep learning during simultaneous bottom-up and top-down signaling.

Cellular and subcellular specialization enables biology-constrained deep learning

Early-life B cell memory is archived in the mouse B-1 cell compartment and drives chronic lymphocytic leukemia-like disease Using a time-stamping approach, Segrén et al. demonstrate that early-life-origin B-1 cells display features of highly differentiated memory, including PD-L2 expression, in the adult context. In a mouse model of unmutated chronic lymphocytic leukemia, B-1 cells that emerge prior to postnatal day 10 account for clonal expansion and disease.

Early-life B cell memory is archived in the mouse B-1 cell compartment and drives chronic lymphocytic leukemia-like disease

Cell Press Symposia: Taking programmed cell death from mechanisms to interventions

Hear directly from the organizers why this is a must-attend event for researchers working on all aspects of cell death and join them in Hangzhou, China, October 22–24, 2026

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Antibacterial microcins self-assemble to promote biofilm formation in Acinetobacter baumannii Telford et al. show a unique role for an antibacterial microcin in structuring biofilm in Acinetobacter baumannii using electron microscopy and biochemical assays. The microcin is shown to form into amyloid fibers that structure biofilm formation, a function that is distinct from its antibacterial action.

Antibacterial microcins self-assemble to promote biofilm formation in Acinetobacter baumannii

UFMylation-dependent inhibition of AKT signaling by PHLDA3 in lung adenocarcinoma Ma et al. demonstrate that UFL1-mediated UFMylation facilitates PHLDA3 membrane localization and restrains AKT signaling in lung adenocarcinoma. A subset of tumor-associated PHLDA3 mutations impairs this modification, leading to AKT hyperactivation. These findings define a tumor-suppressive UFMylation mechanism and highlight the UFL1-PHLDA3-AKT axis as a potential therapeutic vulnerability.

UFMylation-dependent inhibition of AKT signaling by PHLDA3 in lung adenocarcinoma