Research articles

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.

The authors identify a chemical cocktail to generate totipotent-like cells, which they then use to build an embryo model. This model captures a developmental spectrum from early embryogenesis to post-implantation events.

Khawaja et al. show sex-specific differences in neuronal-activity regulation by chaperone-mediated autophagy and that loss of chaperone-mediated autophagy leads to defective neuronal physiology and increased seizure susceptibility, linking chaperone-mediated autophagy to neuronal excitability.

Nguyen, Collier et al. find a mitochondria–lysosome inflammatory pathway regulated by the SUMO E3 ligase MAPL, which promotes vesicular mtDNA transport to lysosomes and subsequent gasdermin-dependent lysosomal permeabilization to activate pyroptosis.

Wu, Zhang and colleagues introduce ‘compare and contrast spatial transcriptomics’ (CoCo-ST), a graph contrastive learning-based method for spatial transcriptomics analysis that detects low-variance structures.

The authors show that the endoplasmic reticulum-phagy receptor FAM134B interacts with SCAP to regulate cholesterol biosynthesis, sequestering SCAP when endoplasmic reticulum cholesterol is high but dissociating upon low cholesterol levels, allowing SCAP to activate cholesterol synthesis.

Mohri et al. show that, in response to genotoxic stress, melanocyte stem cells undergo senescence-associated differentiation, causing their depletion and protecting them against melanomagenesis. This process is suppressed by carcinogens.

The authors integrate single-cell transcriptomic data with prior gene graphs to produce a biologically meaningful cell state manifold that can predict driver genes for genetic perturbations and differentiation events across diverse cell types.

Vanni et al. show a role for microtubules in YAP/TAZ mechanosignalling. Mechanoresponsive microtubule reorganization into centrosomal arrays allows for AMOT delivery to pericentrosomal proteasomes and degradation, leading to YAP/TAZ activation.

Li, He, Liu and colleagues characterize the dynamic bivalent chromatin landscape during mouse peri-implantation development. They find that factor ZBTB17 works with KDM6A/B to resolve transiently maintained bivalent domains and prime gene activation.

Zhang et al. delineate the heterogeneity of core regulatory circuitry in glioblastoma and identify HOXB3 condensation as a vulnerability that may be targeted with a therapeutic peptide in mouse models.

Li, Burgos-Bravo and colleagues report that NDF phase separation regulates FACT condensation, which enhances transcription by generating a localized biochemical environment that promotes nucleosome disassembly while preserving chromatin integrity by retaining histones.

McCreery, Stubb et al. show that mechano-osmotic changes in the nucleus induce general transcriptional repression and prime chromatin for cell fate transitions by relieving repression of specific differentiation genes.

Zhang et al. demonstrate that AMPK can be activated by signalling metabolite, adenosine, under non-stress conditions during Drosophila development. The intestine regulates adenosine levels, thus, remotely controlling wing disc AMPK activation and growth.

Here the authors show that LC3-associated phagocytosis is initiated by various receptors, which enrich phosphatidylserine in the membrane domains proximal to the phagosome, recruiting Rubicon to the membrane for phagosome maturation.

Sun et al. identify a subset of transposable elements that serve as mechano-response enhancer elements that control gene expression and human stem cell fate.

Zhang, Lahry, Cipurko et al. show that the microbial metabolites queuine and preQ₁ modify the same host tRNA. PreQ₁-tRNA reduces cell proliferation, slows tumour growth, decreases the translation of ribosomal proteins and is cleaved by IRE1 on the ER ribosome.

Zheng et al. identify a role for CD160 in regulating CD8⁺ T cell exhaustion and cytotoxicity through the AKT–NF-κB pathway. The transfer of CD160⁺CD8⁺ T cells overcomes resistance to anti-PD-1 treatment in colorectal cancer models.

Al-Hilal, Chrysovergi et al. identify a role for durotaxis in lung fibrosis and metastatic pancreatic cancer, mediated by the FAK–paxillin mechanosensor complex, and demonstrate therapeutic targeting of this pathway using the small molecule JP-153.

Dehingia, Milewska-Puchała and colleagues find a pervasive lncRNA-mediated increase in interactions between CTCF and RNA-binding proteins during embryonic stem cell differentiation. These interactions reinforce chromatin architecture in neural cells.