(Cell Reports 43, 113924; March 26, 2024)

Using genomic approaches, Faiola et al. evaluated the Streptococcus pyogenes carriage state, and pre- and post-treatment pharyngitis, directly from human subjects. This work suggests that carriage isolates may evolve with host-specific mechanisms rather than a unified regulatory phenotype.

Ran et al. identify a heart-associated origin of mouse supraclavicular brown adipose tissue (BAT). Their findings challenge the dominance of interscapular BAT in mouse research and suggest that anatomically corresponding depots may better inform translation to human thermogenic fat.

Delaney et al. show that PAX3::FOXO1 oncofusion-positive rhabdomyosarcoma depends on FANCM to tolerate fusion-associated replication stress. FANCM depletion disrupts the fusion transcriptional program and promotes myogenic differentiation, nominating FANCM as a selective therapeutic target in this rare and aggressive pediatric malignancy.

Agas et al. show that flattening daily glucocorticoid rhythms in mice concentrates insulin resistance in skeletal muscle while preserving key adipose-liver functions. Insulin-responsive fat sequesters lipids and shields the liver, uncoupling profound obesity from hepatic steatosis and recasting hyperinsulinemia as protective rather than pathological.

Fulford et al. show an interaction between butyrophilin (BTN) 3A1 and the δ chain of the Vγ9Vδ2+ T cell receptor. These data suggest that BTN3A1, along with BTN2A1, is sufficient to mediate Vγ9Vδ2+ T cell recognition of phosphoantigen.

Herpes simplex virus (HSV) leads to lifelong infections with potentially severe consequences. Sponholtz et al. use structure-based vaccine design to engineer a prefusion-stabilized HSV-2 gB and explore its use as a vaccine antigen. Antibody and T cell responses from mice immunized with pre- or postfusion gB protein or mRNA are reported.

Das Ghatak et al. demonstrate that soluble factors in S. aureus high biofilm induce MARCOhiMERTKlo macrophage subset niche in human chronic wounds. Such macrophages exhibit impaired efferocytosis through MARCO-CEBP/β-MERTK-signaling axis. These findings reframe biofilm-driven immune subversion as a macrophage subset-level phenomenon and identify MARCO as a mechanistic target for healing chronic wounds.

Akitsu et al. show that clonotype-specific αβ T cell receptor-ligand geometry and force transmission bias cytotoxic T cell memory differentiation within a shared influenza A viral epitope response. Distinct receptor load polarities associate with effector-memory, central-memory, and bipolar outcomes, linking receptor mechanochemistry to memory fate.

Su et al. reveal that BBR, a natural molecular glue degrader, targets HIF1α for TRIM28-mediated ubiquitination and degradation. This targets the PDE4D to deplete glutathione and disables SOD1 via metal dyshomeostasis, synergistically amplifying ROS to trigger ferroptosis and overcome BCR-ABL1-independent resistance.

Perez-Becerra et al. reveal that dorsomedial striatal neurons from the direct and indirect pathways, located in a target region of the primary visual cortex, encode features of visual stimuli in the absence of behavioral contingencies, indicating that the dorsomedial striatum participates in visual information processing, broadening basal ganglia functions.

Pinedo-Bardales, Erreygers et al. combine DNA sequencing techniques and targeted culturing to investigate vaginal microbiome similarity in adult mother-daughter pairs. They confirm significant species-level similarity as well as vaginal strain sharing of lactic acid-producing bacteria, offering insights into the origin and dynamics of the vaginal microbiome.

Gacha-Garay et al. show that BCL2 overexpression blocks developmental apoptosis of mouse lung alveolar myofibroblasts and redirects the fate of these normally transient cells toward their proximal counterpart: ductal myofibroblasts. Both rescued ductal-like and ductal myofibroblasts reactivate contractile genes in an asthma model.

Prolonged high-fat diet exposure during adolescence is detrimental to social recognition memory. Muller et al. show that oxytocin signaling and endocannabinoid plasticity in hippocampal area CA2 undergo detrimental changes with a high-fat diet that can be rescued with oxytocin delivery as well as chemogenetic inhibition.

Li et al. uncover that PD-L1 phosphorylation modulates its recognition by distinct E3 ligases and subsequent proteasomal degradation in heterogeneous tumor. PPM1L dephosphorylates PD-L1, while SERPINB1 adds an extra regulatory tier. PPM1L loss boosts anti-PD-1 immunotherapy, highlighting this axis’s promising translational potential for cancer therapy.

Intercellular mRNA transfer between mammalian cells in vitro occurs via tunneling nanotubes to express functional proteins upon translation that complement genetic mutation. Complementation via RNA transfer is demonstrated for a human disease mutation, gene knockouts, and genetic alterations in a cell-cell contact-dependent manner.

Pittman et al. utilize genetic, biochemical, and structural data to show that type IV-C CRISPR-Cas systems function through DNA targeting. Type IV-C systems do not cleave at the bound target site. Instead, following target binding, the Cas10IVc HD domain nonspecifically cleaves ssDNA and RNA to provide defense against invaders.

(Cell Reports 42, 113391; November 28, 2023)

Zhao et al. show that palmitic acid-induced ACLY C893 palmitoylation stabilizes nuclear ACLY, promoting histone acetylation of pro-inflammatory genes in macrophages. This metabolic-histone modification axis drives anti-tumor immunity. A TAM-targeted LNP delivering PA and shSCD1 (ML-PS) enhances anti-PD-1 therapy, offering a translatable strategy for HCC.

Gao et al. identify an androgen-AR-PDH axis shaping sex differences in visceral adipose mitochondrial function. In male VAT, androgen-AR represses Pdhb transcription, reducing PDH activity and chromatin accessibility at mitochondrial function-related genes, thereby impairing mitochondrial respiration and thermogenesis. PDH activation enhances mitochondrial respiration and reduces visceral adiposity in male mice.

Yang et al. report cryo-EM structures of the CCHFV RNA polymerase across multiple functional states. These structures reveal a promoter-dependent initiation stabilization pathway and a dual-site mechanism of suramin inhibition, providing insights into bunyavirus polymerase regulation and inhibition.

Hennessy et al. identify PACERR as an lncRNA associated with regulation of inflammatory and cholesterol-responsive pathways. PACERR perturbation alters COX-2, ABCA1, and ABCG1 expression, affecting prostaglandin production and cholesterol efflux. These findings support a role for PACERR in coordinating immune and lipid homeostasis relevant to atherosclerosis.

Kobaisi et al. show that the replacement of the native insulin signal peptide with that of chromogranin-A allows human beta cells to evade autoimmune CD8+ T cell destruction while still enabling the production and secretion of functional insulin.

Xu et al. identify a membrane responsive segment in the HLA-A cytoplasmic tail that promotes receptor internalization and limits surface retention. Disrupting this region, genetically or with a tail-derived peptide, reduces internalization and preserves surface HLA-I, revealing a receptor intrinsic mechanism that regulates antigen presenting complex availability.

Lyu et al. show that influenza-driven lactate accumulation induces a tolerogenic dendritic cell state that weakens pulmonary CD8+ T cell responses. Multi-omics and functional analyses link H3K18la-associated NRF2 activation to impaired mtROS-dependent XBP1 splicing and antiviral T cell priming.

Li et al. show that the SARS-CoV-2 SUD2core domain binds the neutrophil protein HEBP2 and recruits the E3 ligase LTN1 to trigger its degradation, thereby activating the Rab27a-SYTL1 axis to drive pathogenic neutrophil degranulation, NETosis, and cytokine release. Small-molecule inhibitors of this interaction attenuate neutrophil-mediated inflammation.

Wu et al. identify GPX3 as a tumor-suppressive regulator in lung adenocarcinoma. By promoting HSPB1 degradation and activating Hippo signaling, GPX3 limits tumor growth and progression. These findings reveal a previously unrecognized molecular pathway and suggest a potential therapeutic strategy for lung adenocarcinoma.

Gorman et al. isolate VRC49, the second Fab-dimerized glycan-reactive, broadly neutralizing antibody recovered from an HIV-infected human since 2G12. Cryo-EM reveals a distinct dimerization mechanism through a CDRH3 disulfide bond forming a wedge that is clamped by nearby glycans, expanding our understanding of how antibodies target the HIV glycan shield.

Zhang et al. show that high glucose triggers AARS1-mediated HDAC1 K412lac, trapping HDAC1 in the cytoplasm and unleashing H3K56ac-VEGFA transcription. Genetic blockade of HDAC1 K412lac protects mice from DR, and the small molecule exifone suppresses this axis—nominating HDAC1 lactylation as a metabolic-epigenetic switch and therapeutic target.

Zhang et al. show that neuroinflammation activates Wnt/β-CATENIN signaling in astrocytes, driving SREBF2-mediated cholesterol synthesis while suppressing APOE-dependent cholesterol efflux. The resulting reduction in cholesterol supply to oligodendrocytes impairs MYRF transcription factor activity and myelin gene expression, which may compromise myelin integrity.

Sun et al. demonstrate that TBK1 stabilizes HDAC3 via Ser424 phosphorylation during Salmonella Typhimurium infection. HDAC3-mediated NDP52 deacetylation at Lys202 enhances its binding to MAP1LC3A/B and GABARAPL2, thereby facilitating intracellular bacterial clearance and host antibacterial defense.

Long-chain fatty acids are often viewed as inhibitors of anammox treatment. This study shows that controlled oleate dosage can promote anammox performance and metabolic flexibility, whereas excessive loading causes membrane damage, defining an operational window for treating organic-rich side-stream wastewater.

Oishi et al. successfully purified influenza PA-X to analyze its host shutoff mechanism using an endonuclease inhibitor. We found that PA-X binds RNA via its C-terminal domain to induce degradation, whereas vRNP assembly protects viral RNAs to selectively modulate the cellular environment.

Our strain-level and species-level analyses showed that the gut microbiome of vaginally delivered infants exhibited higher sharing with the maternal gut or vaginal microbiome, primarily with the gut microbiome. The strain-level analysis showed that sharing frequency varied by species.

Kedan and Zauber et al. combine long-read transcriptomics with molecular-weight-resolved proteomics to generate an integrated landscape of mRNA and protein isoforms. Their IsoFrac framework enables scalable protein isoform discovery, revealing that numerous shorter protein variants contribute substantially to human proteome complexity.

Using Astro-GRASP, researchers discovered that memory formation induces changes in astrocyte-synapse coverage in the cortex. Specifically, astrocytes retract from synapses on non-engram neurons rather than engram neurons long after learning. Reducing the astrocytic coverage enhances remote memory expression, revealing a crucial role for astrocytes in cortical circuitry.

Chen et al. established a cell-based model to investigate mitochondrial recovery after transient damage. They identified the E3 ligase MGRN1 as a mitochondrial repair regulator that is recruited via MFN1 and limits excessive mitophagy, thereby promoting preservation of mitochondria and facilitating recovery through DELE1-eIF2α-ATF4- and Nrf2-mediated antioxidant responses.

Xu et al. show that humans infer hidden rule changes by integrating outcome history with perceptual difficulty during hierarchical reasoning. A confidence-based Bayesian model and RNN capture this process, while human dACC represents errors and difficulty in a near-orthogonal geometry that supports switch-confidence readout and predicts individual performance.

Wang et al. identify a gut-brain pathway in which loss of the commensal bacterium Alistipes shahii reduces indole production, prevents hippocampal indole-AhR signaling, and drives anxiety and depression behaviors in patients and mouse models of irritable bowel syndrome.

Wang et al. report that Menin is essential for corticogenesis. The study reveals that Menin recruits the COMPASS family proteins and deposits H3K4me3 at loci governing neuronal development. This Menin-mediated epigenetic activation of EphA4 promotes neuronal polarization.

Song et al. identify that OTUD1 functions as an RNA-binding protein that stabilizes osteogenic transcripts in mesenchymal stem cells. OTUD1 deficiency drives age- and hormone-induced bone loss. These findings reveal a non-enzymatic function of OTUD1 in bone homeostasis and provide a potential therapeutic target for osteoporosis.

Perez, Schoenfeldt et al. present an integrated platform and methodology combining automation and machine learning to evaluate thousands of conditions across >400 compounds in yeasts, nematodes, flies, killifish, and mice, identifying conserved longevity-associated pathways and prioritizing interventions with strong translational potential.

Using paired genomic and direct in vivo transcriptomic sequencing of human oropharyngeal swabs, Faiola et al. demonstrate that GAS carriage is defined by unique phase-specific gene expression patterns. The results highlight a complex, mechanism of bacterial persistence, and transmission rather than conserved carriage genotypes.

Khan et al. show that long-term nicotinamide riboside produces divergent tissue responses in mitochondrial progeria mice: it restores cardiac NAD+ metabolism and function, but in bone marrow causes redox-metabolic remodeling, transcriptomic stress signatures and disrupted heme/iron pathways and impaired erythroid maturation, highlighting tissue-specific metabolic vulnerabilities when evaluating NAD+ boosting therapies.

(Cell Reports 44, 116363; October 28, 2025)

Epstein-Barr virus (EBV) establishes lifelong latency in human B cells by balancing latent and lytic programs. Dan and Jady et al. show that the viral snoRNA v-snoRNA1 directs 2′-O-methylation at two ribosomal A-site positions, inducing a ribosomopathy-like state that globally rewires gene expression and controls viral production.

This study proposes inferential planning as a framework for understanding frontal neural activity during sequential behaviour. Using active inference models, Donnarumma et al. reproduce key findings from monkey electrophysiology, including the simultaneous representation of multiple plan elements in separable neural subspaces, suggesting that these subspaces may support inferential message passing.

(Cell Reports 44, 115339; March 25, 2025)

Naz et al. benchmark reproducible microglial states across adulthood, aging, and parabiosis to define a conserved activation program and both shared and region-specific transcriptomic remodeling. They further reveal regional differences in microglial sensitivity to parabiosis-mediated accelerated aging and rejuvenation, with the cerebellum the most sensitive and the striatum the least.

Using a broad panel of ciliopathy iPSC-retinal pigment epithelium (RPE) new approach models, Reichert et al. identified shared cellular endophenotypes across patients, including mesenchymal drift and loss of polarization. Mechanistic studies implicated mitochondrial dysfunction and aberrant TGF-β signaling in RPE pathology. Drug screening identified pioglitazone and galunisertib as candidate therapeutics.