This research introduces NeuMap, a comprehensive transcriptional and functional map of the neutrophil compartment developed using single-cell RNA sequencing of mouse and human neutrophils across various tissues and pathological conditions. The study identifies a conserved and finite set of seven distinct transcriptional hubs (e.g., PreNeu, Immuno-silent, IFN-response, and Immunosuppression I/II) that define different functional states of neutrophils. Furthermore, the authors utilize RNA velocity and genetic tracing to map the transcriptional trajectories and dynamics of neutrophils as they mature and respond to conditions like cancer and inflammation, revealing how external signals like cytokines (e.g., GM-CSF, IFN-β) deterministically drive these cells toward specific functional states. The findings establish NeuMap as a valuable diagnostic and research scaffold that can predict host physiological states based on blood neutrophil profiles and facilitate the integration of existing and future neutrophil research data across species.

References:

• Cerezo-Wallis, D., Rubio-Ponce, A., Richter, M. et al. Architecture of the neutrophil compartment. Nature (2025). doi.org

The paper introduces COAST (Consecutive multi-Omics Alignment of Spatial Tissues), a novel computational method for accurately aligning consecutive tissue sections analyzed by different spatial omics technologies. COAST exclusively utilizes paired staining images (like H&E or nuclear stains) to create a shared feature space for alignment, eliminating the need for matching molecular profiles or prior annotations common in other methods. The paper rigorously benchmarks COAST's performance against existing uni-modal alignment tools using spatial transcriptomics data, demonstrating comparable or superior accuracy in preserving tissue structure and achieving high gene expression similarity in matched spots. Finally, the authors illustrate COAST's significant utility by applying it to align spatial transcriptomics and MALDI-MSI data from a mouse kidney injury model, enabling integrated multi-modal analysis that identifies biologically coherent lipid and metabolite features related to specific cell types.

References:

• Image-guided alignment of consecutive multi-modal tissue slides

The article introduces StaVia, a novel computational framework designed for single-cell atlases, which are large datasets detailing cellular states and differentiation. StaVia addresses major challenges in trajectory inference by integrating spatial and temporal metadata with a method utilizing higher-order random walks with memory to accurately trace complex cell lineage pathways. The framework also includes a cartographic Atlas View for intuitive visualization of these large-scale trajectories, outperforming existing methods like UMAP and CellRank in maintaining both global continuity and local separation of cell types. The authors demonstrate StaVia's utility using extensive datasets, including murine gastrulation and the Zebrahub developmental atlas, highlighting its capacity for high-definition, spatially-aware trajectory analysis on complex omics data. The discussion also details the mathematical and algorithmic components underpinning the approach, such as Kernel Density Estimation for edge bundling in visualizations.

References:

• Stassen S V, Kobashi M, Lam E Y, et al. StaVia: spatially and temporally aware cartography with higher-order random walks for cell atlases[J]. Genome Biology, 2024, 25(1): 224.

The paper provides an overview of a research article detailing the creation of a whole-brain, single-cell atlas of circadian neural activity in mice. Researchers used tissue clearing and c-Fos immunostaining over a two-day time series to map the temporal dynamics of spontaneous neural activity across 642 anatomically defined brain regions. The study found that 79% of these regions exhibit significant circadian rhythmicity, with different brain areas, especially those related to sleep-wake cycles, reward, and sensory functions, peaking in activity at diverse circadian times. This comprehensive atlas, made available as an open-access database, allows for predicting the brain's internal circadian time from global activity patterns and provides a vital resource for integrating time-of-day information into neuroscience and pharmacological research.

References:

• Yamashita K, Kinoshita F L, Yoshida S Y, et al. A whole-brain single-cell atlas of circadian neural activity in mice[J]. Science, 2025: eaea3381.

The paper investigates the molecular basis for acquired therapeutic resistance in KRAS-mutant colorectal cancer (CRC) following dual inhibition of KRAS and EGFR. The research establishes that CRC cells utilize lineage plasticity, adopting a secretory Paneth-like cell state to survive the targeted therapy. Mechanistically, this adaptive transition is orchestrated by the SMAD1-FGFR3 signaling axis, which drives resistance by allowing the crucial MAPK pathway to reactivate within the surviving Paneth-like cell population. Through extensive preclinical models and analysis of human patient biopsies, the authors confirm that these resistant cells are significantly enriched after combination treatment. Ultimately, the study demonstrates that co-targeting FGFR3 with the existing dual KRAS-EGFR regimen successfully blocks this Paneth-like transition, offering a viable strategy to enhance anti-tumor efficacy. This discovery highlights the potential of inhibiting the SMAD1-FGFR3 axis to improve outcomes for patients facing resistance to KRAS-targeted therapies.

References:

• Zhang Y, Chen J, She Y, et al. Paneth-like transition drives resistance to dual targeting of KRAS and EGFR in colorectal cancer[J]. Cancer Cell, 2025.

This article by Wang et al. introduces a novel lytic cell death pathway, termed mitoxyperilysis. This process is triggered by the simultaneous occurrence of innate immune activation and metabolic disruption (IIAMD), which together cause mitochondrial oxidative stress and damage. The core mechanistic step, which the authors name mitoxyperiosis, involves damaged mitochondria maintaining prolonged physical contact with the cell's plasma membrane, resulting in lethal local oxidative damage. This sustained contact and subsequent cell death are specifically regulated by the signaling complex mTORC2, which promotes cell lysis by suppressing critical cytoskeletal activity necessary for mitochondrial retraction. Researchers demonstrated that activating the IIAMD synergy can regress tumors in mice, identifying a unique cell death modality that is independent of conventional pathways like pyroptosis or necroptosis. This research suggests a potential strategy for developing mTORC2-dependent cancer therapeutics by manipulating subcellular mitochondrial position.

References:

• Wang Y, Lu J, Carisey A F, et al. Innate immune and metabolic signals induce mitochondria-dependent membrane lysis via mitoxyperiosis[J]. Cell, 2025.

The article examines the intricate mechanism used by umbrella toxins—complex antibacterial particles secreted by Streptomyces—for competition. This mechanism relies on UmbA lectin domains mediating species-specific binding to a novel cell surface carbohydrate receptor: the teichuronic acid-wall teichoic acid (TUA-WTA) hybrid. Resistance studies and cryo-electron microscopy (cryo-EM) confirmed that the toxin's lectin domain specifically recognizes the hypervariable TUA polymer, allowing target cell adhesion. The study concludes that the widespread genomic diversity observed in both the UmbA lectins and the separate internal UmbC toxin domains represents an evolutionary two-tiered molecular bet-hedging strategy. This modular approach allows the bacteria to maintain antagonism against a broad range of changing competitive threats.

References:

• Zhao Q, Vlach J, Park Y J, et al. The unique architecture of umbrella toxins permits a two-tiered molecular bet-hedging strategy for interbacterial antagonism[J]. Cell, 2025.

The paper describes a two-part physiological and immunological mechanism by which acute stress damages hair follicles and triggers autoimmunity. Initially, acute stress causes the sympathetic nervous system to become hyperactivated, releasing excessive norepinephrine which induces a calcium surge that leads to necrosis—or uncontrolled death—of the highly proliferative hair follicle cells (HF-TACs). This immediate necrotic event is highly inflammatory, prompting antigen-presenting cells to capture the resulting cellular debris. Subsequently, this process leads to the activation and expansion of autoreactive CD8+ T cells that are specifically trained to target the hair follicle. Although the tissue recovers from the initial stress, the presence of these primed T cells leaves the body susceptible to future damage. Consequently, a secondary inflammatory trigger, such as an infection or UV exposure, can overcome peripheral tolerance and provoke a secondary, T cell-mediated autoimmune attack against the hair follicles.

References:

• Scott-Solomon E, Brielle S, Mann A O, et al. Stress-induced sympathetic hyperactivation drives hair follicle necrosis to trigger autoimmunity[J]. Cell, 2025.

The article details a structural and pharmacological approach to treating Alzheimer’s disease (AD) by targeting the cholecystokinin B receptor (CCKBR), a G protein-coupled receptor crucial for memory and learning. The authors used cryo-electron microscopy to visualize the CCKBR complex bound to various G protein subtypes (Gq, Gs, and Gi), establishing that distinct receptor conformations are responsible for specific signal bias. This structural information enabled the rational design of synthetic small-molecule ligands, resulting in compounds like the exclusively Gi-biased agonist z-44 and the potent Gq-biased agonist 3r1. Crucially, only the brain-penetrant compound 3r1 demonstrated therapeutic potential in mouse models, significantly improving cognitive function and reducing AD pathology, whereas the Gi-biased agonist had no effect. The beneficial mechanism of 3r1 was identified as the biased activation of the CCKBR-Gq signaling cascade, which promotes neuronal health and reduces plaque formation by upregulating the ADAM10 and PLCB4 proteins.

References:

• Wang J L, Sha X Y, Shao Y, et al. Elucidating pathway-selective biased CCKBR agonism for Alzheimer’s disease treatment[J]. Cell, 2025.

The article explores the connection between mechanical forces, tissue density, and cellular growth control, establishing that membrane potential serves as a fundamental biophysical signal. The authors present a mechano-electro-osmotic model showing that compression leads to higher cytoplasmic biomass density, which physically couples to the cell membrane to induce hyperpolarization. Experimental results confirm that as epithelial tissues reach maximum density, cells become progressively more hyperpolarized and cease proliferation. This electrical signal directly regulates key growth pathways, as hyperpolarization causes the transcriptional co-activator YAP of the Hippo pathway to exit the nucleus, thereby suppressing growth. Conversely, depolarization speeds up wound healing by promoting growth factor activity and YAP nuclear re-entry. This mechanism provides an integrated, size-independent readout of mechanical pressure, which is essential for maintaining tissue homeostasis and preventing tumorous overgrowth.

References:

• Mukherjee A, Huang Y, Elgeti J, et al. Membrane potential mediates the cellular response to mechanical pressure[J]. Cell, 2025.