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Here they perform a systematic dissection of OCT4 and reveal how intrinsically disordered regions can be used to serve specific functions during reprogramming and embryonic development. This can be exploited to engineer more efficient and specific reprogramming factors.

Lipid nanoparticles (LNPs) are a versatile class of clinically approved drug delivery vehicles, particularly for nucleic acid cargoes, but they often suffer from instability issues. Here, the authors report that the room temperature stability of small interfering RNA LNPs formulated with unsaturated ionizable lipids can be improved by inclusion of mildly acidic, antioxidant-containing buffers.

Somatic cells in C. elegans stop dividing after completing their normal lineage at the end of development. Here, Heinze et al. show that constitutive expression of a hox gene prolongs proliferation beyond the restriction imposed by the cell lineage.

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.

Eric Vivier and colleagues discuss the emerging roles for natural killer (NK) cells and other innate lymphoid cell populations in cancer immunity. The authors highlight the current immunotherapy trials that are targeting NK cells to treat patients with cancer.

A significant challenge in modern drug development is the comprehensive profiling of covalent inhibitors. Here, the authors develop COOKIE-Pro, an unbiased method for quantifying the binding kinetics of irreversible covalent inhibitors on a proteome-wide scale.

Lo and colleagues report that double-positive thymocytes from neonates express less Zap70 and show reduced Ca^2⁺/NFAT signaling compared to double-positive thymocytes from older thymi. This diminished Ca^2⁺ signaling alters negative selection for self-reactive TCRs, resulting in a cell-intrinsic temporal window for regulatory T versus conventional T cell development in the thymus.

Mobilization of immature neutrophils (imNeu) can migrate from bone marrow (BM) to circulation and inflamed tissues. However, the mechanism of its mobilization and function remains unknown. Here the authors identify ILC1 mediates IL-10 producing imNeu mobilization to inflamed tissue via IFN-γ, thus tempering the acute inflammation.

Simultaneous profiling of spatial transcriptomics (ST) and metabolomics (SM) offers a novel way to decode tissue microenvironment heterogeneity. Here, the authors present SpatialMETA, a conditional variational autoencoder-based framework designed for the integration of ST and SM data.

Biomolecular condensates are made of multiple components but current techniques cannot capture their complex composition quantitatively. Now it has been shown that the dense-phase binodal point defining the composition of multicomponent condensates can be inferred precisely from the intersection of a spectrometrically determined tie-line with an isorefractive line obtained from quantitative phase imaging.

Previous research has suggested that pDCs are required for an effective antiviral immune response, but direct experimental evidence to support this is lacking. Here Ngo et al. develop a pDC knockin mouse model and find that pDCs are dispensable for an antiviral immune response to mouse cytomegalovirus and may be detrimental during influenza or SARS-CoV-2 infection.

Broad-spectrum vaccines have been proposed as a tool for rapid response to emerging infectious disease threats and are in pre-clinical development. Here, the authors use mathematical modelling to assess the potential impacts of broadly protective sarbecovirus vaccines for a hypothetical “SARS-X” outbreak.

Liang et al. estimate the prevalence of text modified by large language models in recent scientific papers and preprints, finding widespread use (up to 17.5% of papers in computer science).

This study discovers human SERF2 as a key partner in stress granule formation by binding specific RNA G-quadruplexes. SERF2 and these RNAs provide a detailed structural model of protein-RNA interactions driving liquid-liquid phase separation in condensates.

The authors provide a comprehensive characterization of how glutamine uptake and utilization regulate macrophage function in atherosclerosis.

Phaeocystales are ecologically significant nanoplankton whose evolutionary history and functional diversity remain incompletely characterized. Here, the authors integrate genomic and transcriptomic data to reveal their lineage diversification, metabolic plasticity, and adaptation to polar and temperate regimes.

Here the authors reveal a study of 486,956 Han Chinese individuals showing that most people with genetic variants affecting drug response do not have the predicted adverse events, highlighting the challenges of implementing pharmacogenetics in clinical practice.

Analysis of neuroimaging data of people with schizophrenia and healthy controls shows that networks derived from explicitly nonlinear whole-brain functional connectivity exhibit higher reliability than those extracted from linear whole-brain functional connectivity and demonstrate higher sensitivity to the diagnosis of schizophrenia.

Polygenic risk scores can help identify individuals at higher risk of type 2 diabetes. Here, the authors characterise a multi-ancestry score across nearly 900,000 people, showing that its predictive value depends on demographic and clinical context and extends to related traits and complications.

Here the authors perform a trans expression quantitative trait locus meta-analysis study of over 3,700 people and link a USP18 variant to expression of 50 inflammation genes and lupus risk, highlighting how genetic regulation of immune responses drives autoimmune disease and informs new therapies.

How morphogen gradients induce complex gene expression programmes in the receiving cells is poorly understood. Here the authors use a quantitative approach to show that inC. elegansvulva induction cells control morphogen-induced gene expression by changing their sensitivity to the morphogen.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

An understanding of the molecular mechanisms promoting the generation of immunoregulatory and tumour-promoting monocytes and macrophages is key to breaking the cycle of tumour myelopoiesis and developing more effective myeloid-targeting therapies.

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

Many legumes accommodate rhizobial symbionts via transcellular infection threads. Here the authors show that in Medicago root hairs, polar growth of the infection thread requires a tip-localized protein complex consisting of VPY and VPY-like proteins that are stabilized by the E3 ligase LIN, as well as an exocyst complex subunit.

P-selectin has been considered as a biomarker of hematopoietic stem cell (HSC) aging. Here, Yang et al. uncovered a new functional role of P-selectin engagement in regulating HSC regeneration and driving stem cell aging when perturbed.

Blanpain and colleagues delineate lineage reprogramming following PTEN deletion in different prostate cancer-originating cells, demonstrating that in basal cells the NF-κB pathway and innate immunity control stem cell plasticity and tumor initiation.

Foetal haematopoiesis takes place in the liver before the bone marrow is seeded. Here the authors used imaging analysis and mouse genetics to look at nascent bone marrow formation and show that yolk-sac-derived myeloid cells promote haematopoiesis by promoting specification of a VCAM1⁺ sinusoidal colonisation niche.

Let-7 microRNA (miRNA) and its target gene lin-28 regulate pluripotency. A second Let-7 target, lin-41, controls miRNA function in stem cells by regulating the turnover of the miRNA effector Argonaute2 through its ubiquitin ligase activity.

Developing efficient catalysts that resolve the activity-stability trade-off remains challenging for hydrogen production. Here, the authors report a steam-assisted, machine-learning-screened synthesis of self-healing Ru/TiMnO_x electrodes that resolve this challenge.

Graphene-based Josephson junction bolometers hold promise as sensitive single-photon detectors, but they are normally limited by slow readout schemes and narrow operational bandwidths. Here, the authors report the application of Josephson parametric amplifiers as fast, tunable bolometers with sensitivity enhanced by the intrinsic Kerr non-linearity.

Bhandoola and colleagues describe the existence of two pathways of NK cell development that generate functionally distinct NK cell subsets in mice, and which may be conserved in humans.

Spatial transcriptomic studies and lineage tracing reveal that, after brain injury, transient profibrotic fibroblasts develop from existing brain fibroblasts, infiltrate lesions, regulate the local immune response and lead to beneficial scar tissue formation.

This study found higher RSV antibody levels were associated with lower RSV risk in children outside the hospital. An earlier rise in incidence and higher incidence rates were observed among children <5 years compared to older children and adults.

CELLFIE, a CRISPR platform for optimizing cell-based immunotherapies, identifies gene knockouts that enhance CAR T cell efficacy using in vitro and in vivo screens.

This study introduces the Cattle Cell Atlas, a single-cell expression resource including 1,793,854 cells from 59 tissues. Integrative analyses leveraging this atlas provide insights into the biology underlying bovine monogenic and complex traits.

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.

The mechanism of spatiotemporal gene regulation during animal development is a fundamental question in biology. Here the authors show that the DEAD-box helicase DDX-23 controls stem cell fate by driving the formation of NAB repressive transcriptional condensates.

Haematopoietic stem cell numbers are restricted at both systemic and local levels.

Cross-linkable co-SAMs improve hole-selective SAM stability, preventing defects and thermal degredation in perovskite solar cells, enabling 26.92% efficiency with high heat durability, and guiding the design of more efficient and durable solar cells.

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.

The LIN-5/NuMA pathway is needed to correctly position the mitotic spindle for asymmetric division. Now van den Heuvel and colleagues find that polarity kinase aPKC–PKC-3 phosphorylates LIN-5 to direct the localization of the spindle in the early embryos of Caenorhabditis elegans.

Tissue-resident macrophages (TRM) are important mediators of local immunity. Here the authors show that the deficiency or inhibition of a kinase, WNK1, unlinks macrophage colony-stimulating factor signaling and resulted macropinocytosis with the downstream, potentially IRF8-mediated genetic program to bias progenitor differentiation to neutrophil instead of TRM.

Lymphocytes are on high demand during chronic infections. Here, the authors show that human lymphoid precursors, normally found in the bone marrow, circulate in the blood of chronic inflammation patients and give rise to natural killer cells and other lymphocytes.

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.

Trained and validated on multimodal data from 14.5 million images from multicountry datasets, a foundation model is shown to increase diagnostic and referral accuracy of clinicians when used as an assistant in a trial involving 16 ophthalmologists and 668 patients.