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Prostate cancers (PCa) are characterized by an immunosuppressive tumor microenvironment. Here the authors identify a subset of iron-loaded cancer-associated fibroblasts secreting myeloid cell-associated proteins and driving immunosuppression in PCa.

The discovery that DNA methylation of different CpG sites can serve as digital barcodes of clonal identity led to the development of EPI-Clone, an algorithm that enables single-cell lineage tracing through cellular differentiation at scale.

Resources are finite for living organisms; therefore, compromises are required when partitioning resources to different tasks. Here, the authors use the Pareto concept to show how a trade-off is achieved in terms of the performance and metabolic efficiency in a panel of 97 Arabidopsis thalianaaccessions.

Off-the-shelf, on-demand allogeneic CAR-T cells could represent a therapeutic alternative to autologous products for cancer therapy. Here the authors report the preclinical characterization of off-the-shelf CRISPR-Cas9– edited IL-13Rα2-specific allogeneic universal CAR-T cells and the results of a first-in-human phase I trial in patients with high-grade glioma.

Kim, Wang, Clow and colleagues show that long-range chromatin loops bringing distal enhancers or super-enhancers together with promoters are cohesin dependent and cell type specific, whereas most short-range and promoter-centric transcriptional loops are cohesin independent and constitutive.

Liu et al. report Chinese normative lifespan brain charts showing later neurodevelopmental milestones than those detected in Western cohorts. Individual deviations from these norms are valuable in assessing clinical risk and outcomes.

u-Segment3D is a universal framework that translates and enhances 2D instance segmentations to a 3D consensus instance segmentation without training data. It performs well across diverse datasets, including cells with complex morphologies.

Chemically modified and permeabilized bacteria allow for antibiotic delivery inside biofilms, inducing long-term immune protection and eradicating implant-related infections in preclinical models.

Colonna and colleagues show that the clock genes encoding REV-ERBα and REV-ERBβ maintain ILC3 functions in the gut by controlling the expression of RORγt.

China’s crowded coasts must balance seafood demand with conserving migratory shorebirds that rely on tidal flats along the East Asian–Australasian Flyway. This study suggests that well-managed mariculture feeds shorebirds and limits overharvest, benefiting seafood production and biodiversity.

This study leverages plasma proteomics from over 50,000 individuals to build organ-specific aging models and uncover underlying genetic mechanisms. It also investigates causal links between organ aging, diseases, and lifestyle, providing insights for promoting healthy longevity.

The taurine–taurine transporter axis is a critical dependency of aggressive myeloid leukaemias.

Walmsley and colleagues report that systemic hypoxia induces persistent loss of histone H3K4me3 marks and epigenetic reprogramming in neutrophil progenitors, resulting in long-term impairment of subsequent neutrophil effector functions.

The ALICE Collaboration provides details on the microscopic mechanism that ends up creating antideuteron in high-energy proton–proton collisions at the Large Hadron Collider.

De novo and inherited dominant variants in genes encoding U4 and U6 small nuclear RNAs are identified in individuals with retinitis pigmentosa. The variants cluster at nucleotide positions distinct from those implicated in neurodevelopmental disorders.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Nguyen et al. show that the splenic environment provides sequential signals via lymphotoxin and retinoic acid that guide cDC2A development and retention.

Turley and colleagues find that Gremlin1-expressing lymph node fibroblastic reticular cells support dendritic cell homeostasis via provision of FLT3L.

A mechanism is uncovered that results in fetal hepatocytes having a paracrine role in providing genome protection to haematopoietic stem and progenitor cells.

Here the authors unveil the essential role of MCL-1 for adult hair follicle regeneration and inhibition of proliferation stress-induced apoptosis in mice. They also identify a P53/MCL-1/BAK axis balancing proliferation and death of activated hair follicle stem cells to ensure proper hair growth.

Light-responsive polymers with polarization-dependent deformation are promising material to develop tunable devices usually limited by irreversible dynamic control. Here, the authors use controlled polarization of visible light to produce arbitrary deformations into amorphous composites containing azopolymer microdomains to unlock the next level of complex actuation in soft lightdriven robots.

Ganuza et al. report that foetal liver haematopoietic stem cells (HSCs) are largely biased to differentiation rather than self-renewal, resulting in a modest expansion of the HSC pool with contribution to adult haematopoiesis.

This study aims at enhancing hematopoietic stem cell (HSC) gene therapy potential to treat neurodegenerative diseases via innovative approaches. Findings demonstrate the therapeutic benefits of intracerebral transplantation of TREM2-engineered HSCs in an Alzheimer’s disease mouse model.

Human stem cell–derived β cells accumulate high basal PEP, which disrupts glucose-stimulated insulin release. Restoring PKM1 lowers basal PEP and improves glucose responses, advancing the maturation of stem cell–derived islets for diabetes therapy.

After respiratory viral infection and in fibrotic lung disease, repair and remodeling processes particularly affect airway basal cell (BC) and alveolar epithelial cell populations. Here, using single cell transcriptomics and lineage tracing, the authors characterize this process and define roles for innate immune activation in the regulation of BC fate and alveolar remodeling.

The DREPAGLOBE lentiviral-based gene therapy for sickle cell disease is safe. However, its efficacy depends on the number of infused hematopoietic stem cells (HSCs) and intrinsic, engraftment impairing inflammatory alterations in HSCs.

Therapeutic application of hematopoietic stem cells requires a thorough understanding of their in situ differentiation pathways. Here they use single cell proteo-transcriptomic sequencing to identify human HSPC differentiation cues and an immunoregulatory function of CD273/PD-L2 on early HSPCs.

Through integrated multi-omics and experimental validation, this study reveals that altered gut microbiota and bile acid metabolism activate TLR3 to induce urothelial injury in interstitial cystitis, identifying a pathway with therapeutic potential.

A 15-year prospective cohort study found that during times of social unrest in Hong Kong, people experienced more conflicts with family and friends and this coincided with the use of social media—these factors were also associated with higher levels of depression.

This study provides structural insight into the dynamic catalytic mechanism of OsSPS3, a key enzyme in plastoquinone-9 biosynthesis. OsFBN5 enhances the activity of the OsSPS3 dimer by shifting its catalytic mechanism from alternating to synchronous.

Activation of genes depends on transcription factors and chromatin remodelers. Here, the authors show ARID1A organizes these components through phase separation, co-condensing with specific transcription factors to maintain chromatin accessibility and drive gene expression.

It is difficult to image haematopoietic stem cells (HSC) in their niche. Here, the authors present a new high-throughput computational approach to visualise HSCs in vivoat a high spatial and temporal resolution and also use a Msi2-reporter to label endogenous HSCs and progenitors, enabling cell tracking

High-pressure minerals in meteorites reflect the conditions prevailing when they were excavated and launched from their parent bodies. Tissint—a recent Martian meteorite—contains an unusual number of large high-pressure minerals, suggesting excavation from an impact of larger magnitude than for previous Martian samples.

CytoTRACE 2 is an interpretable deep learning framework that leverages single-cell RNA sequencing data to predict absolute developmental potential across datasets.

Metformin may serve as a non-toxic intervention to inhibit mitochondrial metabolism and slow DNMT3A-R882 clonal haematopoiesis expansion, thus delaying or averting progression to acute myeloid leukaemia.

Neutralising antibody levels are an important correlate of protection for pre-exposure prophylaxis against COVID-19, but it can be difficult to account for immune evasion of emerging virus variants. Here the authors present a variant-adjusted threshold of protection model, developed and validated with data from two clinical trials, which can be used to infer efficacy against any SARS-CoV-2 variant.

Multiomic analysis of blast-phase myeloproliferative neoplasms identifies a chromosome 21 amplicon harboring DYRK1A as a clonal and therapeutically targetable event in around a quarter of cases.

Mejía-Ramírez, Iáñez Picazo, Walter et al. explore how nuclear biomechanical changes limit the regenerative capacity of aged hematopoietic stem cells and show that targeting RhoA rejuvenates aged hematopoietic stem cells by reducing nuclear envelope tension and remodeling nuclear architecture.

This study shows that UTX (KDM6A) suppresses myeloid leukemogenesis through noncatalytic functions. UTX loss leads to alterations in H3K27ac, H3K4me1 and chromatin accessibility, and in gene-regulatory programs mediated by ETS and GATA transcription factors.

CD44 expressed by fibroblastic reticular cells in secondary lymphoid organs regulates trafficking of dendritic cells, and thus has an essential role in the priming of T cells and the adaptive immune response.

Genetic inactivation of the plant homeodomain 6 gene (Phf6) counteracts transcriptional and epigenetic aging programs in the hematopoietic system and can reverse the decline of hematopoietic stem cell function associated with age.

The JAK inhibitor ruxolitinib has been used for treatment of myeloproliferative neoplasms (MPN) and its association with clonal evolution requires further investigation. Here the authors report accumulation of RAS pathway mutations in ruxolitinib-treated myelofibrosis patients, stemming from RAS clonal selection induced by JAK2 inhibition.

A combination of biochemical, cell biological and electron microscopy analyses reveal a ‘nucleotide code’ that coordinates Lis1–dynein binding stoichiometry, which in turn governs Lis1’s ability to relieve dynein autoinhibition.