Comprehensive single-cell transcriptomic analysis of 35 human tissues reveals 12 cross-tissue coordinated cellular modules that exhibit intramodule communication and dynamic changes with ageing, and whose organization is perturbed during cancer progression.

Cell type annotation is an essential step in single-cell RNA-sequencing analysis, and numerous annotation methods are available. Most require a combination of computational and domain-specific expertise, and they frequently yield inconsistent results that can be challenging to interpret. Large language models have the potential to expand accessibility while reducing manual input and improving accuracy, but existing approaches suffer from hyperconfidence, hallucinations, and lack of reasoning. To address these limitations, we developed CASSIA for automated, accurate, and interpretable cell annotation of single-cell RNA-sequencing data. As demonstrated in analyses of over 970 cell types, CASSIA improves annotation accuracy in benchmark datasets as well as complex and rare cell populations, and also provides users with reasoning and quality assessment to ensure interpretability, guard against hallucinations, and calibrate confidence. ### Competing Interest Statement The authors have dec

The immune-checkpoint molecule TIM-3 regulates microglial homeostasis, and its microglial-specific deletion reduced cognitive impairment in a mouse model of Alzheimer’s disease.

Hubble Space Telescope data show that the time taken for the planet to revolve around its axis is almost half a minute longer than was thought.

Inflammatory and anti-inflammatory cytokines act as neuromodulators to regulate anxiety levels via direct action on the same population of neurons in the amygdala of mice, underscoring the conservation of immune signaling and its receptor subunits in the brain.

STING signaling in the innate immune system is well known for its role in the antiviral type I interferon response. Tang et al. find that STING acts as an immune sensor of lysosomal activity. When the...

Using a mouse tumor model with inducible cGAS expression, Herbst et al. show that cancer-cell-derived cGAMP triggers a sustained type I interferon response, enhancing CD8+ T cell-dependent tumor restr...

How tumor cells overcome anti-tumor immune responses and drive cancer recurrence is not well understood. Yu et al. demonstrate how therapy-resistant breast cancer cells synthesize and secrete arachido...

Deleting a regulatory element in the Rorc gene depletes RORγt+ dendritic cells from the intestine in mice, leading to a reduction of regulatory T cells and impaired oral tolerance to antigens. This work clarifies that RORγt+ DCs are key to maintaining intestinal immune balance and preventing inappropriate immune responses to food antigens.

By integrating single-cell RNA and physically interacting cell sequencing analysis, here Cohen and colleagues report that neutrophils are enriched in physical crosstalk with breast tumor cells, promot...

How tumor cells overcome anti-tumor immune responses and drive cancer recurrence is not well understood. Yu et al. demonstrate how therapy-resistant breast cancer cells synthesize and secrete arachidonic acid-rich lipids to reprogram tumor-infiltrating neutrophils. These immunosuppressive tumor-associated neutrophils promote T cell exhaustion and enable cancer cells to escape therapeutic immunosurveillance.