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Li et al. characterize overlapping and divergent metabolic requirements of human and murine NK cells in response to activation, with a focus on serine metabolism

Preventing endosomal damage sensing or using lipids that create reparable endosomal holes reduces inflammation caused by RNA–lipid nanoparticles while enabling high RNA expression.

Addition of an inexpensive, biocompatible polymer reduces spontaneous fusions of organoids in culture.

Ataluren restored SBDS protein synthesis in three patients with Shwachman-Diamond syndrome, improving bone marrow cellularity and pancreatic function without side effects, highlighting its potential as therapeutic option for this genetic disease.

Primary antiphospholipid syndrome (PAPS) is a clotting disorder attributed to autoreactive antibodies produced by B cells. Here the authors show, using single cell omics and B cell repertoire data, that autoreactive B cells originate from the natural B cell repertoire and escape germinal center selection to persist in PAPS patient via potential dysregulation of mTORC1 and MYC pathways.

Anandasabapathy and colleagues show that the inhibitory receptor PD-1 impacts the specification of tissue-resident memory T cells in the skin.

Hegazy and colleagues demonstrate that epithelial oncostatin M receptor expression drives gut inflammation and tumor formation.

O-GlcNAc transferase (OGT) mediates antiviral host immune response. Here, the authors identify a catalytic activity-independent function of OGT in restraining influenza A virus replication by translocating to lipid droplets and limiting their accumulation following interaction with viral RNA.

In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

Miyoshi and colleagues propose STELLA-SPIM microscopy to visualise single MYO7A molecules in live murine inner ear hair cells. Their data suggest that MYO7A traffics as a dimer within stereocilia to assemble the mechanoelectrical transduction machinery.

Proliferative vitreoretinopathy (PVR) is a vision-threatening response to ocular injury, in which retinal cells secrete tractional, scar-forming proteins. Here, the authors show that antibody blockade of either Annexin A2 or its inducer, macrophage inflammatory protein-1, prevents PVR in mice.

Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

A single dose of an adeno-associated virus vector encoding an HIV-1 broadly neutralizing antibody given shortly after birth results in persistent antibody expression and protection from infection in rhesus macaque models of human HIV-1 transmission through breastfeeding and sexual intercourse.

Here the authors show that lab mice have retained ancient gut bacterial symbionts that diversified in parallel with rodent species, but the genomes of these gut bugs have accumulated mutational burdens over the past ~ 120 years of inbreeding in captivity.

The transcription factors TCF1 and LEF1 promote self-renewal and regulatory functions in B-1a cells.

With increasing river flow, sand dunes on the riverbed initially grow and eventually flatten out. However, flume experiments show that dune height distributions under high flow are bimodal, suggesting flickering between high and low dune heights.

Collagen can be a metabolic source to fuel cancer growth. Here the authors show that cell surface protein TEM8 mediates the binding and uptake of collagen in stromal cells and these cells processed the collagen to glutamine, providing an alternative energy source for tumour cells to grow.

Circulating tumor cell (CTC) clusters are much more likely to produce viable metastasis than single CTCs. Here the authors find that the transmembrane protein Plexin-B2 (PLXNB2) mediates homotypic and heterotypic CTC cluster formation, driving lung metastasis in breast cancer mouse models.

This study uses chromatin tracing to identify alterations in single-cell 3D genome conformation during the progression of Kras-driven mouse lung adenocarcinoma and pancreatic ductal adenocarcinoma, and proposes Rnf2 as a regulator of the 3D genome.

In response to acute thermal challenge, thermosensing glutamatergic neurons of the parabrachial nucleus in mouse brain activate tanycytes, which reduce the excitability of Flt1-expressing dopamine and agouti-related peptide-containing neurons, thus suppressing appetite.

Clonal hematopoiesis is driven by the selective advantage of mutant hematopoietic stem cells. Here, authors discover that elevated mitochondrial activity is a targetable mechanism by which mutant hematopoietic stem cells gain a selective advantage.

Nasal anti-CD3 therapy shows promise for treating traumatic brain injury by reducing neuroinflammation and aiding recovery in mice. It induces interleukin-10-producing regulatory T cells that enhance microglial phagocytic activity and reduce chronic inflammation, potentially aiding brain repair.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

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.

This study, together with a companion manuscript, shows that in mice, weight loss as a result of GIP receptor antagonism requires and potentiates functional GLP-1 receptor signalling in the brain, explaining how both GIP receptor agonists and antagonists trigger weight loss through different mechanisms.

Missense mutations in the twelfth codon of KRAS are key drivers of lung cancer. Here, the authors develop a CRISPR-High Fidelity-Cas9-based strategy to target KRAS-G12C and KRAS-G12D mutants, reducing tumourigenicity without wild type KRAS off-targeting and circumventing certain therapy resistance mechanisms in preclinical models.

In this study, the authors describe SANA, a nitroalkene derivative of salicylate, as a potential activator of creatine-dependent energy expenditure and thermogenesis in adipose tissue. Preclinical and clinical data from this paper also suggest that SANA improves glucose homeostasis and promotes weight loss in mice and humans.

Here, the authors show that KDM2A regulates cell cycle progression, modulation of H3K36me2 and H3K27me3 chromatin states and gene repression which are critical for survival of differentiating spermatogonia. KDM2A regulates progression through meiosis as well.

A DNA matrix material potentiates humoral response through multiple administration routes, generating neutralizing antibodies and conferring robust protection against infection.

Here they show that HDAC6 inhibition regulates fumarate hydratase (FH), disrupts mitochondria, increases fumarate, and causes cancer cell death. This suggests that HDAC6 inhibition could be a strategy to target tumour metabolism indirectly.

Pathological B-cell receptor (BCR) signaling is a key driver of mantle cell lymphoma tumorigenesis. Here, the authors discover that CEACAM1, an immunoglobulin-like transmembrane protein, is essential for a subset of mantle cell lymphoma through activation of the BCR.

Patients who express a hyperactive mutant of the kinase PI3K exhibit defective humoral immunity. Preite et al. show that overactive PI3K leads to defective class-switched antigen-specific responses to immunization, despite augmented germinal-center formation and reactivity to commensal microbes and self antigens.

The molecular mechanisms of cell entry for the recently identified highly pathogenic feline coronavirus FCoV-23 are characterized in detail.

Few studies have suggested that enteric glial cells (EGCs) promote colorectal cancer growth. Here the authors show that EGC-derived IL-6 promotes the expansion of tumorigenic SPP1⁺ tumor-associated macrophages, associated with worse disease outcome.

SARS-CoV-2 infection can lead to sustained increased macrophage numbers and formation of enlarged lipid-laden macrophages after viral clearance. This can be prevented with antiviral treatment in mice.

Hydrogel materials have emerged as versatile platforms for biomedical applications. Here this group reports an mRNA lipid nanoparticle-incorporated microgel matrix for immune cell recruitment/antigen expression and presentation/cellular interaction thereby eliciting antitumor efficacy with a single dose.

Understanding the brain’s diversity requires spatially resolved maps of transcripts and proteins. Here, the authors construct an integrated molecular atlas of the mouse hippocampus revealing local enrichment profiles and compartmental organization.

Molecular recorders based on kinase activity-dependent protein labeling track specific kinase activities to understand their link to cellular phenotypes in heterogeneous cell populations and in vivo.

This paper reports a customizable CRISPR ribonucleoprotein delivery tool, dubbed RIDE, for the treatment of Huntington’s disease in mice, non-human primates and patients’ iPSC neurons.

Hypoimmune gene editing in human pluripotent stem cells (hPSCs) provides a promising platform for cellular therapies. Here, the authors report that CRISPR mediated deletion of ICAM-1 in hPSC-derived grafts reduces immune cell adhesion, dampens T cell activation, and protects against immune rejection.

Kaluba, Rogers et al. show that in cancer cells that can metabolize ketones, they may reroute them to produce cytosolic acetyl-CoA and support tumour growth.

In Drosophila, coherent slow-wave activity between sleep-promoting and locomotion-promoting neural networks provides a brain state structure that allows for quiescent behaviours.

Spatial cell distribution within a tissue microenvironment is a rapidly advancing field. Here, authors assess three commercially available single-cell resolution spatial transcriptomics approaches (CosMx, MERFISH, and Xenium) to inform which technology outperforms for immune profiling of solid tumors using patient samples.