scBaseCount is presently the largest public single-cell RNA-seq repository, containing over 502 million cells across 27 organisms and 75 tissues. An AI agent autonomously discovers, annotates, and uniformly reprocesses all 10× Genomics datasets in the SRA, creating a harmonized, continually updated resource for studying the diversity of cell biology and training AI models.

LongevityBench, Longevity-LLMs, and Longevity Claw evaluate the readiness of the state-of-the-art AI systems for spearheading aging research.

Agarwal et al. introduce MitoSpace, a self-supervised model trained on 4D lattice light-sheet microscopy data. The model resolves drug-induced mitochondrial phenotypes without labels, predicts membrane potential from morphology and dynamics, generalizes to unseen perturbations and lung organoids, and shows that representation quality improves progressively from 2D to 4D.

Modeling perturbation effects across large single-cell populations requires flexibility to capture heterogeneity. By training over sets of cells in a shared embedding space, State outperforms baselines at generalizing effects to new contexts. Cell-Eval, the framework used for this comparison, provides a comprehensive benchmark for future models.

Drawing inspiration from Hilbert’s list of 23 mathematical problems that have focused the mathematical community’s attention for more than a century, we propose fifteen grand AI challenges to focus the biomedical community’s attention on critically relevant questions, most of which still lack effective predictive methodologies.

Spatial multi-omics reveals macrophage states that constrain adaptive immunity in immunosuppressed non-melanoma skin cancer.

Arginine availability regulates arginyl tRNA levels and codon-dependent translation of MHC class I, tuning antigen presentation and shaping anti-viral and anti-tumor immunity.

Sprox-seq enables spatial profiling of protein complexes, surface proteins, and mRNAs in intact tissues by combining proximity ligation with spatial transcriptomics. In human tonsils, Sprox-seq maps germinal center interaction networks, links CD21-CD35 complexes to proliferative programs, reveals interaction-based B cell state transitions, and directly captures B cell-follicular dendritic cell communication.

Fibrosis is a major contributor to disease and mortality yet lacks effective therapies. This review proposes that fibrotic states are maintained by chromatin-regulated circuits in fibroblasts and macrophages shaped by immune-stromal crosstalk and that rewiring this upstream regulatory logic offers a path beyond current antifibrotic approaches.

The Drosophila whole male central nervous system connectome enables end-to-end analysis of sensorimotor circuits. Comparison with existing female datasets shows that brain-wide wiring differences between the sexes are concentrated in higher centers.

PD-1+ T follicular helper-like cells drive B cell-associated pathology in multiple sclerosis. Programmable PD-1-targeting CAR T cells selectively eliminate these pathogenic CD4 T cells while delivering IL-10 at sites of inflammation, thereby suppressing neuroinflammation across preclinical models.

Chemically induced proximity of lysine acetyltransferases (KATs) with BCL6 reprograms epigenetic signaling to eliminate lymphoma tumors. Structural and mechanistic studies demonstrate that fortuitous protein-protein contacts convert proximity induction into targeted changes in chromatin, revealing a key mechanism by which small molecules can co-opt oncogenic transcriptional regulators to elicit malignant cell death.

Multiomics profiling of healthy individuals reveals differences across molecular layers and key pathways related to immune, metabolic, and microbiome-linked processes across ethnicities, while geographic relocation reshapes these networks and influences aging trajectories.

An optogenetic model of accelerated intermittent theta burst stimulation reveals cell type-specific plasticity mechanisms and a key role for a fronto-insular circuit in driving the antidepressant effects of this treatment in humans.

Cancers evade RAS-targeting molecular glues through distinct alterations that converge on disrupting synthetic complex formation, exposing strategies for improved drug design and rational combination therapy.

Opposing oncogenic and tumor-suppressive forces establish a progenitor-like state that builds a self-reinforcing niche to drive benign-to-malignant transition in pancreatic cancer models. Disruption of p53 activity or KRAS inhibits malignancy by collapsing the niche.

Gallego-del-Sol et al. show that arbitrium-coding phages can sense non-cognate peptide signals from other phages to regulate lysis-lysogeny decisions. This crosstalk affects lysis-lysogeny outcomes of phage infections, mixed lysogenic communities, and polylysogens. Our results demonstrate that crosstalk is an important mechanism that drives phage interactions in microbial communities.

Synergizing with senescence-inducing therapies, uPAR CAR T cells eradicate primary and metastatic solid tumors with minimal myelodepletion by targeting both tumor cells and the stroma in preclinical models.

A pan-neurodegeneration atlas built from multilayer, deep proteomics of 2,279 brain samples across 6 major diseases integrates whole proteome, detergent-insoluble proteome, and posttranslational modifications to enable intra- and inter-disease comparisons to reveal disease-specific subtypes and dysregulated pathways, while identifying shared changes such as GPNMB upregulation and NPTX2 downregulation.

A platform called MIST enables quantification and genotyping of infectious influenza in expelled respiratory particles, revealing diverse, individual-specific viral loads and aerosolized variants that correlate with saliva and nasopharyngeal viral loads and symptoms. Overall, the findings indicate heterogeneity in transmission potential.