News & Views

Bu using organ-wide single-cell MERFISH, researchers create a spatial atlas of healthy human skin and identify distinct site-specific cellular compositions. This work emphasize the importance of skin organization, from molecular architecture to anatomical scales, in maintaining skin homeostasis and influencing patterns of disease.

In this issue, Jiang et al. introduce a proteomic method called LoopID and show that JMJD2 demethylases have a non-catalytic role in promoting enhancer–promoter looping in mouse embryonic stem cells. This function is mediated by their intrinsically disordered domains, suggesting a condensate-based mechanism.

Current diagnostic work-up and management of thyroid nodules and cancer leads to unnecessary investigations and suboptimal treatment. This study provides insights into the genetic basis of thyroid cancer, including the potential application of polygenic risk scores across multiple stages of thyroid cancer screening, diagnosis and management.

Understanding how infections reshape the human immune system requires integration of environmental, genetic and cellular sources of variability. Wang et al. leverage natural infection as a shared perturbation to reveal how genetic backgrounds modulate epigenetic responses.

A study reveals how chromosomal instability and resultant TP53 loss enhance fatty acid metabolism to drive breast cancer brain metastasis. This metabolic dependency provides new insights into therapeutic vulnerabilities of aneuploid tumors.

A study using single-cell 3D genome mapping reveals phenotypic convergence during mouse Kras-driven lung adenocarcinoma progression and prioritizes clinically actionable driver genes. This highlights the importance of cell-to-cell variation in chromatin architecture as a determinant of cancer evolution.

Creative use of informed statistical genetics methods combined with large-scale genomic data has delivered insights about sorting into educational fields. This study has wide-ranging implications for geneticists, sociogenomicists and social scientists for what can be learned about society within genetic data.

A study drawing on biobank and registry data from five Nordic countries reveals distinct genetic associations for early- and late-onset major depressive disorder and differences in their genetic architectures and relationships with other traits. Stratification by age at onset can uncover risk effects relevant to severe outcomes and inform prevention strategies.

The epigenetic underpinnings of memory are still poorly understood. A study provides a causal link between the epigenetic dynamics of a single genomic locus in engram cells and memory formation, achieved by the development of a reversible epigenetic editing tool.

Spatial transcriptomics enables the characterization of diverse cell types with increasing resolution while retaining the spatial context of complex tissues. A study combines single-cell and spatial ‘spot’-based transcriptome measurements to identify cell states in the developing human heart and define spatial relationships within cardiac niches.

The transcription factors responsible for initiating embryonic genome activation (EGA) in humans remain largely unknown. A study now characterizes the role of the maternal factor OTX2 in kickstarting human EGA.

Using integrated single-cell multi-omics and spatial analysis, this study identifies a PRRX1-driven GPR116⁺ pericyte subpopulation that promotes tumor metastasis and immune evasion in esophageal squamous cell carcinoma, offering a diagnostic biomarker and potential therapeutic strategies.

Human centromeres contain a small chromatin region with low levels of DNA cytosine methylation that resides with CENP-A. Salinas-Luypaert et al. find a role of DNA methylation in maintaining the size and function of centromeres by controlling the binding affinity of key centromere components.

Bryophytes are a widespread group of land plants that occupy nearly all biomes, yet their genetics and evolutionary history have long remained underexplored. Now, a study that generates extensive genomic data for bryophytes highlights de novo gene formation and horizontal gene transfer as key forces that shape bryophyte diversity and adaptation.

A newly uncovered mechanism shows how a single transposable element of retroviral origin can adopt the expression pattern of a neighboring gene. This leads to the production of viral-like particles that disrupt organ formation when epigenetic silencing is compromised.

Two complementary studies used whole-genome sequencing of single cell-derived hematopoietic colonies to show that chemotherapy results in a marked decrease in hematopoietic stem and progenitor cell (HSPC) diversity, with the parallel evolution of multiple independent HSPCs harboring mutations in DNA damage response genes.

How primary gallbladder tumors evolve to acquire immunosuppressive and pro-metastatic capabilities remains unclear. A study using single-cell RNA sequencing coupled with spatial profiling and functional experiments has pinpointed mechanisms of immune-mediated tumor cell reprogramming, fostering disease progression.

Shigella is a major human pathogen with a stark lack of pipelines linking genome content to clinical pathogenesis. An innovative study using large-scale organoid models, combined with genome-wide mutagenesis screening, reveals virulence factors required for Shigella colonization.

Enhancer sequences evolve rapidly, which has led to the prevailing view that most are not functionally conserved across species. A study now challenges this assumption by leveraging interspecies point projection — a method that uses genome synteny to uncover hidden enhancer conservation.

CRISPR–Cas base editing of trinucleotide repeats shows promise in reducing somatic repeat expansions in Huntington’s disease and Friedreich’s ataxia, offering a potential new therapeutic strategy.