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Insights into regulatory T cell biology are accelerating therapeutic innovation in cancer immunotherapy, autoimmune diseases and transplant rejection.

The authors identify Nuclear receptor subfamily 6 group A member 1 (Nr6a1) as a master regulator of elongation, segmentation, patterning and lineage allocation specifically within the trunk region of the mouse, acting downstream of the major signals known to control vertebral column formation.

Bång-Rudenstam et al. report that the acidic tumour microenvironment facilitates the assembly of chondroitin sulfate-enriched glycocalyx to disrupt lipid scavenging and prevent ferroptosis, thereby providing an adaptive mechanism upon tumour acidosis.

In the adrenal cortex, cholesterol used for steroid production is stored in lipid droplets. The authors demonstrate here the importance of the transcription factor HHEX in maintaining glucocorticoid levels and protecting lipid droplets from androgen-induced lipid depletion.

The authors investigate the heterogeneity of Toxoplasma bradyzoites prior to recrudescence. Tissue cysts from infected mice harbor multiple bradyzoite subtypes with distinct developmental fates as evidenced by single-bradyzoite RNAseq and FACS.

Patin and colleagues present a mineable Resource database for identifying demographic and genetic factors that impact antiviral antibody repertoires in humans.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Lipid nanoparticle based mRNA vaccines are known to induce robust CD4 + T cell responses. Here the authors establish a role of endogenously derived antigen processing in the optimal priming of CD4 + T cell responses to mRNA lipid nanoparticle vaccines.

Stem cells in the pituitary master gland remain mystifying; moreover, they have hardly been explored in humans. A new study applied transcriptome and chromatin accessibility profiling at single-cell resolution to human postmortem pituitary glands from individuals of different ages, thereby providing insights into the heterogeneity and regulatory mechanisms of the projected human pituitary stem cell population.

The high-plasticity cell state (HPCS) is a critical hub that enables reciprocal transitions between cancer cell states, and targeting the HPCS may suppress cancer progression and eradicate treatment resistance.

Laser-induced tuning of pairs of lifetime-limited organic emitters allows the controlled creation of superradiant and subradiant entangled states.

Colorectal cancer is often diagnosed at later stages, leading to poor prognosis. Here, the authors utilise analysis of rectal mucus specimens using host and microbial analysis to detect cancer lesions.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

The authors show that increased Xist RNA levels can induce de novo silencing of genes that normally escape X inactivation. SPEN depletion prevents the silencing of escape genes upon Xist RNA overexpression in neural progenitors.

Coordinated gene segment rearrangement across a long genomic distance is essential for antibody gene production, but how this is regulated at the chromatin level is still unclear. Here the authors show that an architectural protein, CTCF, modulates both chromatin loop extrusion and diffusion to enforce diverse Vκ gene segment utilization for a diverse Igκ repertoire.

The study introduces scFFPE-ATAC, a high-throughput single-cell chromatin accessibility profiling method enabling profiling from clinically archived formalin-fixed paraffin-embedded (FFPE) tissues, unlocking retrospective epigenetic insights across cancer and human diseases.

Building scalable quantum technologies requires generating robust many-body entanglement in solid-state platforms. This Review highlights how engineered light–matter interactions, optical nonlinearities and coupling to nanophotonic structures enable coherent many-body entangled states that are resilient to disorder and decoherence.

α/β-hydrolase domain-containing protein 11 (ABHD11) is a mitochondrial hydrolase, and its expression in CD4 + T-cells has been linked to remission status in rheumatoid arthritis. Here the authors report that pharmacological inhibition of ABHD11 modulates T-cell effector function via increased 24,25-epoxycholesterol biosynthesis and subsequent liver X receptor activation.

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.

Understanding the mechanisms underlying the survival of drug tolerant persister cells following chemotherapy remains elusive. Here, multi-omics analysis and experimental approaches show that the germ-cell-specific H3K4 methyltransferase PRDM9 promotes metabolic rewiring in glioblastoma stem cells.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Approaches combining genetic association and Perturb-seq data that link genetic variants to functional programs to traits are described.

PU.1^low CD28-expressing microglia may act as suppressive cells in Alzheimer’s disease, mitigating its progression by reducing neuroinflammation and amyloid plaque load, indicating potential immunotherapeutic approaches for treatment.

Here the authors show that gut metagenomes of Indigenous Australian infants living remotely, display greater diversity and abundance of bacteria, viruses and fungi, compared to non-Indigenous infants living in urban Australia, suggesting that while having access to Western foods, the infants start life with a gut microbiome that retains key features of pre-industrialized societies.

This Article details the methods used for rigorous assessment of disease interventions in a multicenter preclinical trial. Using stroke models as proof of concept, it offers adaptable protocols for any field requiring robust preclinical validation.

Encouraging academics to act as advisers to outside organizations is the most effective way to serve society’s needs.

There is still a need for effective HIV vaccines. In this phase I clinical trial, the authors show that an HIV-1 vaccine candidate, ConM SOSIP.v7, is well-tolerated in HIV-negative adults and that it elicits a strain-specific neutralising antibody response that differed between female and male participants.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

The authors reveal that, in fruit fly ovaries, the protein Rhino is guided to specific regions of the genome by a combination of two histone modifications, enhancing understanding of how cells protect their DNA from harmful virus-like elements.

A retrospective, observational study shows that completion of a diabetes prevention program in England (the NHS Diabetes Prevention Programme) was associated with decreased incidence of type 2 diabetes and long-term conditions such as dementia and chronic obstructive pulmonary disease at 24 months.

A metabolic system of engineered biocatalysts using the noncanonical cofactor nicotinamide mononucleotide is established for biomanufacturing in cell-free systems and in Escherichia coli without interference from nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate.

DIAL designs synthetic promoters for generation of heritable setpoints of gene expression across a range of cell types.

Long-distance migration and dispersion is a common characteristic of nearly all classes of telencephalic GABAergic neurons, which diversify extensively after birth in the cortex and striatum, but show limited postnatal changes in the septum, preoptic area and pallidum.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

A mass spectrometry-based approach globally identifies protein regulators of metabolism and reveals the role of LRRC58 in controlling cysteine catabolism.

The thymus is sensitive to acute insults including infection, as well as to injury from chemotherapy and myeloablative conditioning before hematopoietic cell transplantation. Here, Granadier et al. describe a role for IL-18 in limiting thymic regeneration by stimulating NK cells, which then target thymic epithelial cells.

This multi-omic longitudinal analysis of the healthy human peripheral immune system constructs the Human Immune Health Atlas and assembles data on immune cell composition and state changes with age, including responses to cytomegalovirus infection and influenza vaccination.

This study found E. coli phylogenetic background shapes TEM-1 beta-lactamase expression and co-amoxiclav resistance. Phylogeny alone shifted isolates from susceptible to resistant, stressing a need for lineage-sensitive genotype-phenotype prediction.

Microglia can help clear amyloid β plaques in the Alzheimer’s disease brain but may also become dysfunctional and can contribute to disease progression. March-Diaz et al. reveal that hypoxia, a potentially modifiable risk factor for Alzheimer’s disease, disrupts the metabolism and function of microglia near plaques, which may contribute to neuropathology.

A study of SARS-CoV-2 variants examining their transmission, infectivity, and potential resistance to therapies provides insights into the biology of the Delta variant and its role in the global pandemic.

The response of prostate cancer cells to androgens depends on the dose. Here, the authors show that low levels of androgens function through androgen receptor (AR) monomers to activate mTOR and promote cell proliferation, while high dose androgens induce AR dimerization to inhibit c-MYC expression and facilitate cell differentiation.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

A quantitative morphological framework for the human thymus reveals the establishment of the lobular cytokine network, canonical thymocyte trajectories and thymic epithelial cell distributions in fetal and paediatric thymic development.

Constitutional mismatch repair deficiency (CMMRD) is associated with high cancer incidence early in life. Here, the authors perform a genomic analysis of CMMRD-associated tumors and find mutational patterns influenced by the affected mismatch repair gene, tumour type, and treatment history.

In a combined analysis of two large patient cohorts, three peripheral consensus transcriptomic subtypes of sepsis are identified, which can be linked to an 18-gene classifier associated with different odds of mortality and may offer a way to tailor care for patients with sepsis.

This study analysed genetic data of soil-transmitted helminths from 27 countries, revealing diversity impacting molecular test accuracy and highlighting the need to adapt diagnostics for effective STH surveillance.