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Using flow cytometry and single-cell RNA-sequencing, the authors here describe immune signatures defined by dysfunctional NK and T-cell responses that discriminate patients who develop severe dengue infection from those with uncomplicated dengue.

Watt, Dauber, Szkop and colleagues find that H3K4me3 remodels 5′UTR selection in hypoxia and that this process is independent of HIF-1 transcriptional mechanisms.

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.

Batlle and colleagues report that after chemotherapy, Mex3a⁺ colorectal cancer cells represent drug-tolerant persister cells that lead to recurrence by downregulating the WNT–Lgr5⁺ stem cell program and adopting a transient regenerative state.

The authors perform meta-analysis of GWAS studies for asthma from multiancestral cohorts. They identify five new loci and find that the asthma-associated loci are enriched near enhancer marks in immune cells.

In B-cells, super-silencers originally help activate important genes during early development. Later, they switch roles and become powerful silencers in mature B cells. Super-silencers help control gene activity in healthy B-cells, but when they malfunction or mutate, they may drive the development of B-cell cancers. In healthy, mature B cells, super-silencers keep developmental genes switched off to maintain cell identity. When disrupted by mutation or malfunction, these elements can reverse their role and contribute to the development of B-cell cancers.

Schumacher and colleagues have designed a reporter system that allows in vivo tracking of replicative history over many cell generations. Using this system to study acute T cell responses, they uncover substantial diversity in past division of central memory CD8⁺ T cells and its link to cell state and recall potential.

A new version of nanorate DNA sequencing, with an error rate lower than five errors per billion base pairs and compatible with whole-exome and targeted capture, enables epidemiological-scale studies of somatic mutation and selection and the generation of high-resolution selection maps across coding and non-coding sites for many genes.

Basal-like breast cancer is a heterogeneous disease with poor prognosis; however, its cellular origins and aetiology are poorly understood. Here the authors provide evidence that ID4 is a key controller of mammary stem/progenitor cell self-renewal, acting upstream of Notch signalling to repress luminal fate commitment.

TFE3-fusions are known to drive both epithelial and mesenchymal renal tumors. Here, the authors generate a transgenic mouse model of renal tumorigenesis expressing the human SFPQ-TFE3 fusion, showing that the fusion regulates mTORC1 activity and induces lineage plasticity.

R-loops formed by RNA hybridization to DNA template strand during transcription influence HIV-1 integration into the CD4⁺ T cell genome. The unwinding of R-loops by splicing helicase Aquarius facilitates integration into speckle-associated domains.

Head and neck squamous cell carcinoma (HNSCC) frequency and risk factors vary considerably across regions and ancestries. Here, the authors conduct a multi-ancestry genome-wide association study and fine mapping study of HNSCC subsites in cohorts from multiple continents, finding susceptibility and protective loci, gene-environment interactions, and gene variants related to immune response.

Indonesian cattle are unique due to their history of admixture involving both zebu and banteng. Here, Wang et al. identify ~3.5 million novel introgressed SNP variants and provide a genomic map of banteng introgression within and across many cattle breeds, each with unique introgression histories.

Here the authors use a range of approaches to examine the interplay between genetic variants linked to risk for polygenic skin diseases and transcription factors (TFs) important for skin homeostasis. The findings implicate dysregulated binding of specific TF families in risk for diverse skin diseases.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

Heller et al. showed dense longitudinal imaging in four females, including one with endometriosis and one using oral contraceptives, and the finding that different hormonal milieus influence widespread brain volume changes linked to progesterone or estradiol.

The nuclear localization of metabolic enzymes is fascinating and in most cases remains a mystery. Here, Pardo Lorente and colleagues show that nuclear MTHFD2 is required for successful mitosis by controlling centromeric histone methylation.

Patients with different small round cell sarcoma (SRCS) often receive the same treatment regimen but for some SRCS subtypes, response to chemotherapy is poor and targeted treatment options are limited. Here, the authors establish a biobank of paediatric patient-derived SRCS tumoroids and perform drug screening, identifying MCL inhibition as a potential therapeutic strategy in CIC::DUX4 sarcomas.

The majority of human genes can produce multiple isoforms, but studying their functional relevance requires tools to target specific isoforms. Here, the authors develop a CRISPR-based exon-exon junction-targeting strategy to achieve isoform-specific RNA knockdown.

Integration of snATAC-seq and snRNA-seq data from brains of individuals with major depressive disorder identifies chromatin accessibility alterations and functional enrichment of risk variants in deep-layer excitatory neurons. Gray matter microglia in these individuals show decreased accessibility at sites bound by regulators of immune homeostasis.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

Mechanical confinement of cancer cells at the tumour–microenvironment interface induces phenotype switching through chromatin remodelling by HMGB2, leading to a more invasive and drug-resistant state in melanoma.

Here the authors apply machine learning approaches to Alzheimer’s genetics, confirm known associations and suggest novel risk loci. These methods demonstrate predictive power comparable to traditional approaches, while also offering potential new insights beyond standard genetic analyses.

Trees in cold climates, as revealed by Zhang et al., utilize the proteins PHYB and PIF4 to precisely time their winter dormancy, allowing them to grow under fluctuating temperatures without ceasing growth too early. This unique adaptation enhances forest resilience in a changing climate by optimizing seasonal growth and minimizing frost damage.

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

BindCraft, an open-source, automated pipeline for de novo protein binder design with experimental success rates of 10–100%, leverages AlphaFold2 weights to generate binders with nanomolar affinity without the need for high-throughput screening.

Khan et al. report a non-catalytic function of the methyltransferase SETD2 in regulating nuclear morphology and genome integrity. The SETD2 amino terminus functions as a scaffold helping CDK1 associate with lamins during nuclear-envelope disassembly

KDM4C regulates cathepsin L-mediated histone H3 N-terminal tail clipping through grainyhead-like 2 (GRHL2) methylation in breast cancer. This link between the cellular redox state and chromatin remodeling might represent a therapeutic target in KDM4C-amplified tumors.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

A minimal effector subset enables Salmonella Typhimurium to overcome bottlenecks regulated by the early innate immune response and establish infection within a CD62L⁺ monocyte niche in the spleen.

Transcription factors shape cell identity, but mapping their genomic targets remains challenging. Here the authors present DynaTag, a modified CUT&Tag method for profiling TF occupancy in bulk and single cells, and apply it to assess changes in TF activity in SCLC tumours following chemotherapy.

Pioneer neurons extend their axons to provide a track for follower neurons to follow, whether these neurons differ in other ways has not been clear. Here they show that pioneer and follower neurons are transcriptionally distinct and that RA signaling is required for pioneer axon targeting.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

Experimental characterization of the pathways by which the carbapenemase KPC-2 evolves high activity against ceftazidime reveals strong epistasis underpinning four major resistance groups, each with distinct phenotypic profiles that may shape the enzyme’s long-term success.

Here the authors conduct a multi-ancestry meta-analysis of telomere length, used diverse approaches to identify genes underlying association signals, and experimentally validated POP5 and KBTBD6 as regulators of telomere length in human cells.

MORC2, a chromatin remodeler involved in epigenetic silencing and DNA repair, is linked to cancer and neurological disorders when dysregulated. Here, the authors show that MORC2 binds DNA at multiple sites, clamps onto it, and induces compaction, a process regulated by its phosphorylation.

Genomic, single-cell transcriptomic and epigenetic analyses show that chaetognaths, following extensive gene loss in the gnathiferan lineage, relied on newly evolved genes and lineage-specific tandem duplications, not caused by a whole-genome duplication event, to shape their distinctive body plan.

Single-cell multi-omics in Drosophila testis reveals enhancer-driven gene regulatory networks and shows how Wnt signaling and key transcription factors orchestrate stem cell maintenance and lineage progression during early spermatogenesis.

Nature Biotechnology’s annual survey highlights academic startups that are, among other things, designing circular RNA therapeutics, tackling cancer with arenaviruses, creating psychedelics without the trip, editing genes and cells in vivo, harnessing the power of autoantibodies and editing the epigenome.

Conducting a simulated turtlegrass herbivory experiment across 650 experimental plots and 13 seagrass meadows, the authors show that the negative effects of herbivory increase with latitude, driven by low levels of light insolation at high latitudes.

Beyond its known role in stabilizing microtubules, it is now shown that tau protein actively promotes lattice defect repair by enhancing tubulin turnover at topological defects.

Blanc et al. uncover how chronic inflammation triggers an epigenetic switch in aged muscle stem cells, leading to iron accumulation and cell death by ferroptosis—offering insights into muscle aging and potential paths for regenerative therapies.

Age is a risk factor for SARS-CoV-2 infection and severe disease. Here the authors perform DNA methylation analyses in whole blood from COVID-19 patients using established epigenetic clocks and telomere length estimators, and describing correlations between epigenetic aging and the risk of SARS-CoV-2 infection and severe disease.

DNA methylation is an epigenetic mark that plays a critical role in many biological processes. Here, we describe the development of SAM-DNMT3A a tool for induction of genome wide DNA methylation. Using SAM-DNMT3A we show that DNA methylation is a unique vulnerability in ER+ breast cancer.